Biotrauma: Signal Transduction and Gene Expression in the Lung

  • Claudia C. dos Santos
  • Mingyao Liu
  • Arthur S. Slutsky
Part of the Molecular and Cellular Biology of Critical Care Medicine book series (MCCM, volume 1)

Abstract

Mechanical injury due to artificial ventilation has been thought to play a role in lung injury for over 250 years (1). However, only recently has it become apparent that this injury is likely not confined to the lung alone, but it may contribute to the development of multi-system organ failure (MSOF) in patients with acute respiratory distress syndrome (ARDS) (2). The major cause of death in patients with ARDS is multiple organ failure, not hypoxia (3). There is little doubt that mechanical ventilation can physically disrupt the lung (4, 5). However, in addition to structural damage, it has been postulated that mechanical ventilation can also induce changes in the activation and recruitment of inflammatory cells, and stimulate the production of a number of inflammatory mediators (2). One theory, is that by altering both the pattern and magnitude of stretch, mechanical ventilation may lead to alterations in gene expression and/or cellular metabolism, ultimately leading to the development of an overwhelming generalized inflammatory response that may eventually lead to MSOF and/or death. This mechanism of injury has been termed biotrauma (2, 6).

Keywords

Permeability Torque Dexamethasone Prostaglandin Pseudomonas 

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References

  1. 1.
    Fothergill J. (1745) Observations on a case published in the last volume of the medical essays, & c. of recovering a man dead in appearance, by distending the lungs with air. Philos Trans R Soc Lond 43, 275–281Google Scholar
  2. 2.
    Tremblay, L.N., and Slutsky, A.S. (1998) Ventilator-induced injury: from barotrauma to biotrauma. Proc Assoc Am Physicians 110, 482–488PubMedGoogle Scholar
  3. 3.
    Montgomery, A.B., Stager, M.A., Carrico, C.J., and Hudson, L.D. (1985) Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 132, 485–489PubMedGoogle Scholar
  4. 4.
    Dreyfuss, D., Soler, P., and Saumon, G. (1992) Spontaneous resolution of pulmonary edema caused by short periods of cyclic overinflation. J Appl Physiol 72, 2081–2089PubMedGoogle Scholar
  5. 5.
    Dreyfuss, D., Soler, P., and Saumon, G. (1995) Mechanical ventilation-induced pulmonary edema. Interaction with previous lung alterations. Am J Respir Crit Care Med 151, 1568–1575PubMedGoogle Scholar
  6. 6.
    Slutsky, A.S., and Tremblay, L.N. (1998) Multiple system organ failure. Is mechanical ventilation a contributing factor? Am J Respir Crit Care Med 157, 1721–1725PubMedGoogle Scholar
  7. 7.
    ARDS Network. (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network N Engl J Med 342, 1301–1308CrossRefGoogle Scholar
  8. 8.
    Slutsky, AS. (1999) Lung injury caused by mechanical ventilation. Chest 116, 9S–15SCrossRefGoogle Scholar
  9. 9.
    John, E., McDevitt, M., Wilborn, W., and Cassady, G. (1982) Ultrastructure of the lung after ventilation. Br J Exp Pathol 63, 401–407PubMedGoogle Scholar
  10. 10.
    Parker, J.C., Hernandez, L.A., and Peevy, K.J. (1993) Mechanisms of ventilator-induced lung injury. Crit Care Med 21, 131–143PubMedCrossRefGoogle Scholar
  11. 11.
    Fu, Z., Costello, M.L., Tsukimoto, K., Prediletto, R., Elliott, A.R., Mathieu-Costello, O., and West, J.B. (1992) High lung volume increases stress failure in pulmonary capillaries. J Appl Physiol 73, 123–133PubMedGoogle Scholar
  12. 12.
    Dreyfuss, D., and Saumon, G. (1998) Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 157, 294–323PubMedGoogle Scholar
  13. 13.
    Liu, M., and Post, M. (2000) Invited review: mechanochemical signal transduction in the fetal lung. J Appl Physiol 89, 2078–2084PubMedGoogle Scholar
  14. 14.
    Liu, M., Tanswell, A.K., and Post, M. (1999) Mechanical force-induced signal transduction in lung cells. Am J Physiol 277, L667–L683PubMedGoogle Scholar
  15. 15.
    Wirtz, H.R., and Dobbs, L.G. (2000) The effects of mechanical forces on lung functions. Respir Physiol 119, 1–17PubMedCrossRefGoogle Scholar
  16. 16.
    dos Santos, C.C., and Slutsky, A.S. (2000) Invited review: mechanisms of ventilator-induced lung injury: a perspective. J Appl Physiol 89, 1645–1655PubMedGoogle Scholar
  17. 17.
    Sachs, F. (1992) Stretch-sensitive ion channels: an update. Soc Gen Physiol Ser 47, 241–260PubMedGoogle Scholar
  18. 18.
    Ghazi, A., Berrier, C., Ajouz, B., and Besnard, M. (1998) Mechanosensitive ion channels and their mode of activation. Biochimie 80, 357–362PubMedCrossRefGoogle Scholar
  19. 19.
    Parker, J.C., Ivey, C.L., and Tucker, J.A. (1998) Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs. J Appl Physiol 84, 1113–1118PubMedCrossRefGoogle Scholar
  20. 20.
    Liu, M., Xu, J., Tanswell, A.K., and Post, M. (1994) Inhibition of mechanical strain-induced fetal rat lung cell proliferation by gadolinium, a stretch-activated channel blocker. J Cell Physiol 161, 501–507PubMedCrossRefGoogle Scholar
  21. 21.
    Xu, J., Liu, M., Liu, J., Caniggia, I., and Post, M. (1996) Mechanical strain induces constitutive and regulated secretion of glycosaminoglycans and proteoglycans in fetal lung cells. J Cell Sci 109, 1605–1613PubMedGoogle Scholar
  22. 22.
    Mourgeon, E., Isowa, N., Keshavjee, S., Zhang X., Slutsky, A.S., and Liu, M. (2000) Mechanical stretch stimulates macrophage inflammatory protein-2 secretion from fetal rat lung cells. Am J Physiol Lung Cell Mol Physiol 279, L699–L706PubMedGoogle Scholar
  23. 23.
    Martin, D.K., Bootcov, M.R., Campbell, T.J., French, P.W., and Breit, S.N. (1995) Human macrophages contain a stretch-sensitive potassium channel that is activated by adherence and cytokines. J Membr Biol 147, 305–315PubMedGoogle Scholar
  24. 24.
    Waters, C.M., Ridge, K.M., Sunio, G., Venetsanou, K., and Sznajder, J.I. (1999) Mechanical stretching of alveolar epithelial cells increases Na(+)-K(+)- ATPase activity. J Appl Physiol 87, 715–721PubMedGoogle Scholar
  25. 25.
    Hong, K., and Driscoll, M. (1994) A transmembrane domain of the putative channel subunit MEC-4 influences mechanotransduction and neurodegeneration in C. elegans. Nature 367, 470–473PubMedCrossRefGoogle Scholar
  26. 26.
    Huang, M., and Chalfie, M. (1994) Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans. Nature 367, 467–470PubMedCrossRefGoogle Scholar
  27. 27.
    Lai, C.C., Hong, K., Kinnell, M., Chalfie, M., and Driscoll, M (1996) Sequence and transmembrane topology of MEC-4, an ion channel subunit required for mechanotransduction in Caenorhabditis elegans. J Cell Biol 133, 1071–1081PubMedCrossRefGoogle Scholar
  28. 28.
    Vlahakis, N., and Hubmayr, R. (2000) Cellular responses to mechanical stress: plasma membrane stress failure in alveolar epithelial cells. J Appl Physiol 89, 2490–2496PubMedGoogle Scholar
  29. 29.
    Sayeed, M.M. (1996) Alterations in calcium signaling and cellular responses in septic injury. New Horiz 4, 72–86PubMedGoogle Scholar
  30. 30.
    Hinman, L.E., Beilman, G.J., Groehler, K.E., and Sammak, P.J. (1997) Wound-induced calcium waves in alveolar type II cells. Am J Physiol 273, L1242–L1248PubMedGoogle Scholar
  31. 31.
    Grembowicz, K.P., Sprague, D., and McNeil, P.L. (1999) Temporary disruption of the plasma membrane is required for c-fos expression in response to mechanical stress. Mol Biol Cell 10, 1247–1257PubMedGoogle Scholar
  32. 32.
    Bajpai, A., Andrews, G.K., and Ebner, K.E. (1989) Induction of c-fos mRNA in rat lymphoma Nb-2 cells. Biochem Biophys Res Commun 165, 1359–1363PubMedCrossRefGoogle Scholar
  33. 33.
    Ghosh, A., and Greenberg, M.E. (1995) Calcium signaling in neurons: molecular mechanisms and cellular consequences. Science 268, 239–247PubMedCrossRefGoogle Scholar
  34. 34.
    Tremblay, L., Valenza, F., Ribeiro, S.P., Li, J., and Slutsky, A.S. (1997) Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest 99, 944–952PubMedCrossRefGoogle Scholar
  35. 35.
    Dawes, N.J., Cox, V.M., Park, K.S., Nga, H., and Goldspink, D.F. (1996) The induction of c-fos and c-jun in the stretched latissimus dorsi muscle of the rabbit: responses to duration, degree and re-application of the stretch stimulus. Exp Physiol 81, 329–339PubMedGoogle Scholar
  36. 36.
    Sadoshima, J., and Izumo, S. (1993) Mechanotransduction in stretch-induced hypertrophy of cardiac myocytes. J Recept Res 13, 777–794PubMedGoogle Scholar
  37. 37.
    Kawata, A., and Mikuni-Takagaki, Y. (1998) Mechanotransduction in stretched osteocytes—temporal expression of immediate early and other genes. Biochem Biophys Res Commun 246, 404–408PubMedCrossRefGoogle Scholar
  38. 38.
    Roelofsen, J., Klein-Nulend, J., and Burger, E.H. (1995) Mechanical stimulation by intermittent hydrostatic compression promotes bone-specific gene expression in vitro. J Biomech 28, 1493–1503PubMedCrossRefGoogle Scholar
  39. 39.
    Ballermann, B.J., Dardik, A., Eng, E., and Liu, A. (1998) Shear stress and the endothelium. Kidney Int Suppl 67, S100–S108PubMedCrossRefGoogle Scholar
  40. 40.
    McNeil, P.L., and Steinhardt, R.A. (1997) Loss, restoration, and maintenance of plasma membrane integrity. J Cell Biol 137, 1–4PubMedCrossRefGoogle Scholar
  41. 41.
    Muthukrishnan, L., Warder, E., and McNeil, P.L. (1991) Basic fibroblast growth factor is efficiently released from a cytosolic storage site through plasma membrane disruptions of endothelial cells. J Cell Physiol 148, 1–16PubMedCrossRefGoogle Scholar
  42. 42.
    Ingber, D.E. (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol 59, 575–599PubMedCrossRefGoogle Scholar
  43. 43.
    Tschumperlin, D.J., Fredberg, J.J., and Drazen, J.M. (2000) Mechanotransduction via specific cell-matrix interactions in airway epithelial cells. Am J Respir Crit Care Med 161, A259Google Scholar
  44. 44.
    Wang, N., Butler, J.P., and Ingber, D.E. (1993) Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127PubMedCrossRefGoogle Scholar
  45. 45.
    Peake, M.A., Cooling, L.M., Magnay, J.L., Thomas, P.B., and El Haj, A.J. (2000) Selected contribution: regulatory pathways involved in mechanical induction of c-fos gene expression in bone cells. J Appl Physiol 89, 2498–2507PubMedGoogle Scholar
  46. 46.
    Hubmayr, R.D., Shore, S.A., Fredberg, J.J., Planus, E., Panettieri, R.A., Moller, W., Heyder, J., and Wang, N. (1996) Pharmacological activation changes stiffness of cultured human airway smooth muscle cells. Am J Physiol 111, C1660–C1668Google Scholar
  47. 47.
    Bhullar, I.S., Li, Y.S., Miao, H., Zandi, E., Kim, M., Shyy, J.Y., and Chien, S. (1998) Fluid shear stress activation of IkappaB kinase is integrin-dependent. J Biol Chem 273, 30544–30549PubMedCrossRefGoogle Scholar
  48. 48.
    Oberholzer, A., Oberholzer, C., and Moldawer, L.L. (2000) Cytokine signaling— regulation of the immune response in normal and critically ill states. Crit Care Med 28, N3–12PubMedCrossRefGoogle Scholar
  49. 49.
    Keane, M.P., and Strieter, R.M. (2000) Chemokine signaling in inflammation. Crit Care Med 28, N13–N26PubMedCrossRefGoogle Scholar
  50. 50.
    Ingber, D.E. (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol 59, 575–599PubMedCrossRefGoogle Scholar
  51. 51.
    Russo, L.A., Ranneis, S.R., Laslow, K.S., and Rannels, D.E. (1989) Stretch-related changes in lung cAMP after partial pneumonectomy. Am J Physiol 257, E261–E268PubMedGoogle Scholar
  52. 52.
    Liu, M., Xu, J., Souza, P., Tanswell, B., Tanswell, A.K., and Post. M. (1995) The effect of mechanical strain on fetal rat lung cell proliferation: comparison of two- and three-dimensional culture systems. In Vitro Cell Dev Biol Anim 31, 858–866PubMedCrossRefGoogle Scholar
  53. 53.
    Liu, M., Xu, J., Liu, J., Kraw, M.E., Tanswell, A.K., and Post, M. (1995) Mechanical strain-enhanced fetal lung cell proliferation is mediated by phospholipase C and D and protein kinase C. Am J Physiol 268, L729–L738PubMedGoogle Scholar
  54. 54.
    Chess, P.R., Toia, L., and Finkelstein, J.N. (2000) Mechanical strain-induced proliferation and signaling in pulmonary epithelial H441 cells. Am J Physiol Lung Cell Mol Physiol 279, L43–L51PubMedGoogle Scholar
  55. 55.
    Quinn, D., Tager, A., Joseph, P.M., Bonventre, J.V., Force, T., and Hales, C.A. (1999) Stretch-induced mitogen-activated protein kinase activation and interleukin-8 production in type II alveolar cells. Chest 116, 89S–90SCrossRefGoogle Scholar
  56. 56.
    Kito, H., Chen, E.L., Wang, X., Ikeda, M., Azuma, N., Nakajima, N., Gahtan, V. and Sumpio, B.E. (2000) Role of mitogen-activated protein kinases in pulmonary endothelial cells exposed to cyclic strain. J Appl Physiol 89, 2391–2400PubMedGoogle Scholar
  57. 57.
    Waters, C.M., Savla, U., and Panos, R.J. (1997) KGF prevents hydrogen peroxide-indueed increases in airway epithelial cell permeability. Am J Physiol 272, L681–L689PubMedGoogle Scholar
  58. 58.
    Wang, H.C., Zentner, M.D., Deng, H.T., Kim, K.J., Wu, R., Yang, P.C., and Ann, D.K. (2000) Oxidative stress disrupts glucocorticoid hormone-dependent transcription of the amiloride-sensitive epithelial sodium channel alpha-subunit in lung epithelial cells through ERK-dependent and thioredoxin-sensitive pathways. J Biol Chem 275, 8600–8609PubMedCrossRefGoogle Scholar
  59. 59.
    Dlugosz, J.A., Munk, S., Kapor-Drezgic, J., Goldberg, H.J., Fantus, I.G., Scholey, J.W., and Whiteside, C.I. (2000) Stretch-induced mesangial cell ERK1/ERK2 activation is enhanced in high glucose by decreased dephosphorylation. Am J Physiol Renal Physiol 279, F688–F697PubMedGoogle Scholar
  60. 60.
    Irigoyen, J.P., Besser, D., and Nagamine, Y. (1997) Cytoskeleton reorganization induces the urokinase-type plasminogen activator gene via the Ras/extracellular signal-regulated kinase (ERK) signaling pathway. J Biol Chem 272, 1904–1909PubMedCrossRefGoogle Scholar
  61. 61.
    Reusen, H.P., Chan, G., Ives, H.E., and Nemenoff, R.A. (1997) Activation of JNK/SAPK and ERK by mechanical strain in vascular smooth muscle cells depends on extracellular matrix composition. Biochem Biophys Res Commun 237, 239–244CrossRefGoogle Scholar
  62. 62.
    Nguyen, H.T., Adam, R.M., Bride, S.H., Park, J.M., Peters, C.A., and Freeman, M.R. (2000) Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells. Am J Physiol Cell Physiol 279, C1155–C1167PubMedGoogle Scholar
  63. 63.
    Pan, J., Fukuda, K., Saito, M., Matsuzaki, J., Kodama, H., Sano, M., Tkahashi, T., Kato, T., and Ogawa, S. (1999) Mechanical stretch activates the JAK/STAT pathway in rat cardiomyocytes. Circ Res 84, 1127–1136PubMedCrossRefGoogle Scholar
  64. 64.
    Bhattacharya, S., Ying, X., Fu, C., Patel, R., Kuebler, W., Greenberg, S. and Bhattacharya, J. (2000) alpha(v)beta(3) integrin induces tyrosine phosphorylation-dependent Ca(2+) influx in pulmonary endothelial cells. Circ Res 86, 456–462Google Scholar
  65. 65.
    Liu, M., Qin, Y., Liu, J., Tanswell, A.K., and Post, M. (1996) Mechanical strain induces pp60src activation and translocation to cytoskeleton in fetal rat lung cells. J Biol Chem 271, 7066–7071PubMedCrossRefGoogle Scholar
  66. 66.
    Parker, J.C., Ivey, C.L., and Tucker, A. (1998) Phosphotyrosine phosphatase and tyrosine kinase inhibition modulate airway pressure-induced lung injury. J Appl Physiol 85, 1753–1761PubMedGoogle Scholar
  67. 67.
    MacGillivray, M.K., Cruz, T.F., and McCulloch, C.A. (2000) The recruitment of the interleukin-1 (IL-1) receptor-associated kinase (IRAK) into focal adhesion complexes is required for IL-1beta -induced ERK activation. J Biol Chem 275, 23509–23515PubMedCrossRefGoogle Scholar
  68. 68.
    Ranjan, V., Xiao, Z., and Diamond, S.L. (1995) Constitutive NOS expression in cultured endothelial cells is elevated by fluid shear stress. Am J Physiol 269, H550–H555PubMedGoogle Scholar
  69. 69.
    Uematsu, M., Ohara, Y., Navas, J.P., Nishida, K., Murphy, T.J., Alexander, R.W., Nerem, R.M., and Harrison, D.G. (1995) Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 269, C1371–C1378PubMedGoogle Scholar
  70. 70.
    Awolesi, M.A., Sessa, W.C., and Sumpio, B.E. (1995) Cyclic strain upregulates nitric oxide synthase in cultured bovine aortic endothelial cells. J Clin Invest 96, 1449–1454PubMedCrossRefGoogle Scholar
  71. 71.
    Savla, U., Sporn, P.H., and Waters, C.M. (1997) Cyclic stretch of airway epithelium inhibits prostanoid synthesis. Am J Physiol 273, L1013–L1019PubMedGoogle Scholar
  72. 72.
    Blackwell, T.S., and Christman, J.W. (1997) The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol 17, 3–9PubMedGoogle Scholar
  73. 73.
    Lentsch, A.B., Czermak, B.J., Bless, N.M., Van Rooijen, N., and Ward, P.A. (1999) Essential role of alveolar macrophages in intrapulmonary activation of NF-kappaB. Am J Respir Cell Mol Biol 20, 692–698PubMedGoogle Scholar
  74. 74.
    Du, W., Mills, I., and Sumpio, B.E. (1995) Cyclic strain causes heterogeneous induction of transcription factors, AP-1, CRE. binding protein and NF-κB, in endothelial cells: species and vascular bed diversity. J Biomech 28, 1485–1491PubMedCrossRefGoogle Scholar
  75. 75.
    Schwartz, M.D., Moore, E.E., Moore, F.A., Shenkar, R., Moine, P., Haenel, J.B. and Abraham, E. (1996) Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome. Crit Care Med 24, 1285–1292PubMedCrossRefGoogle Scholar
  76. 76.
    Pugin, J., Dunn, I., Jolliet, P., Tassaux, D., Magnenat, J.L., Nicod, L.P. and Chevrolet, J.C. (1998) Activation of human macrophages by mechanical ventilation in vitro. Am J Physiol 275, L1040–L1050PubMedGoogle Scholar
  77. 77.
    Held, H.D., Boettcher, S., Hamann, and L., Uhlig, S. (2001) Ventilation-Induced chemokine and cytokine release is associated with activation of nuclear factor-kappaB and is blocked by steroids. Am J Respir Crit Care Med 163, 711–716PubMedGoogle Scholar
  78. 78.
    Beutler, B. (2000) Endotoxin, toll-like receptor 4, and the afferent limb of innate immunity. Curr Opin Microbiol 3, 23–28PubMedCrossRefGoogle Scholar
  79. 79.
    van Deventer, S.J. (2000) Cytokine and cytokine receptor polymorphisms in infectious disease. Intensive Care Med 26, S98–102PubMedCrossRefGoogle Scholar
  80. 80.
    Poltorak, A., He, X., Smirnova, I., Liu, M.Y., Huffel, C.V., Du, X, Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi-Castagnoli, P., Layton, B., and Beutler, B. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085–2088PubMedCrossRefGoogle Scholar
  81. 81.
    Takata, M., Abe, J., Tanaka, H., Kitano, Y., Doi, S., Kohsaka, T., and Miyasaka, K. (1997) Intraalveolar expression of tumor necrosis factor-alpha gene during conventional and high-frequency ventilation. Am J Respir Crit Care Med 156, 272–279PubMedGoogle Scholar
  82. 82.
    Imai, Y., Kawano, T., Miyasaka, K., Takata, M., Imai, T., and Okuyama, K. (1994) Inflammatory chemical mediators during conventional ventilation and during high frequency oscillatory ventilation. Am J Respir Crit Care Med 150, 1550–1554PubMedGoogle Scholar
  83. 83.
    von Bethmann, A.N., Brasch, F., Nusing, R., Vogt, K., Volk, H.D., Muller, K.M., Wendel, A., and Uhlig, S. (1998) Hyperventilation induces release of cytokines from perfused mouse lung. Am J Respir Crit Care Med 157, 263–272Google Scholar
  84. 84.
    Kawano, T., Mori, S., Cybulsky, M., Burger, R., Ballin, A., Cutz, E., and Bryan, A.C. (1987) Effect of granulocyte depletion in a ventilated surfactant-depleted lung. J Appl Physiol 62, 27–33PubMedGoogle Scholar
  85. 85.
    Chiumello, D., Pristine, G., and Slutsky, A.S. (1999) Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome. Am J Respir Crit Care Med 160, 109–116PubMedGoogle Scholar
  86. 86.
    Haitsma, J.J., Uhlig, S., Goggel, R., Verbrugge, S.J., Lachmann, U., and Lachmann, B. (2000) Ventilator-induced lung injury leads to loss of alveolar and systemic compartmentalization of tumor necrosis factor-alpha. Intensive Care Med 26, 1515–1522PubMedCrossRefGoogle Scholar
  87. 87.
    Ranieri, V.M., Suter, P.M., Tortorella, C, De Tullio, R., Daye, J.M., Brienza, A, Bruno, F. and Slutsky, A.S. (1999) Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 282, 54–61PubMedCrossRefGoogle Scholar
  88. 88.
    Dreyfuss, D., and Saumon, G. (1998) From ventilator-induced lung injury to multiple organ dysfunction? Intensive Care Med 24, 102–104PubMedCrossRefGoogle Scholar
  89. 89.
    Millar, A.B., Foley, N.M., Singer, M., Johnson, N.M., Meager, A., and Rook, G.A. (1989) Tumour necrosis factor in bronchopulmonary secretions of patients with adult respiratory distress syndrome. Lancet 2, 712–714PubMedCrossRefGoogle Scholar
  90. 90.
    Moldawer, L.L., and Minter, R.M. (2000) Tumor necrosis factor-alpha and the development of multiple organ failure. Crit Care Med 28, 2158–2159PubMedCrossRefGoogle Scholar
  91. 91.
    Bone, R.C. (1996) Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation. Crit Care Med 24, 163–172PubMedCrossRefGoogle Scholar
  92. 92.
    Sadikot, R.T., Christman, J.W., and Blackwell, T.S. (2000) Chemokines and chemokine receptors in pulmonary diseases. Curr Opin Investig Drugs 1, 314–320PubMedGoogle Scholar
  93. 93.
    Pugin, J., Ricou, B., Steinberg, K.P., Suter, P.M., and Martin, T.R. (1996) Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS, a prominent role for interleukin-1. Am J Respir Crit Care Med 153, 1850–1856PubMedGoogle Scholar
  94. 94.
    Verbrugge, S.J., Sorm, V., van’t Veen, A., Mouton, J.W, Gommers, D., and Lachmann, B. (1998) Lung overinflation without positive end-expiratory pressure promotes bacteremia after experimental Klebsiella pneumoniae inoculation. Intensive Care Med 24, 172–177PubMedCrossRefGoogle Scholar
  95. 95.
    Narimanbekov, I.O., and Rozycki, H.J. (1995) Effect of IL-1 blockade on inflammatory manifestations of acute ventilator-induced lung injury in a rabbit model. Exp Lung Res 21, 239–254PubMedCrossRefGoogle Scholar
  96. 96.
    Shibata, Y., Nakamura, H., Kato, S., and Tomoike, H (1996) Cellular detachment and deformation induce IL-8 gene expression in human bronchial epithelial cells. J Immunol 156, 772–777PubMedGoogle Scholar
  97. 97.
    Ding, A.H., Porteu, F., Sanchez, E., and Nathan, C.F. (1990) Shared actions of endotoxin and taxol on TNF receptors and TNF release. Science 248, 370–372PubMedCrossRefGoogle Scholar
  98. 98.
    Manie, S., Schmid-Alliana, A., Kubar, J., Ferrua, B., and Rossi, B. (1993) Disruption of microtubule network in human monocytes induces expression of interleukin-1 but not that of interleukin-6 nor tumor necrosis factor-alpha. Involvement of protein kinase A stimulation. J Biol Chem 268, 13675–13681PubMedGoogle Scholar
  99. 99.
    Bedard, M., McClure, C.D., Schiller, N.L., Francoeur, C., Cantin, A., and Denis, M. (1993) Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis. Am J Respir Cell Mol Biol 9, 455–462PubMedGoogle Scholar
  100. 100.
    Okada, M., Matsumori, A., Ono, K, Furukawa, Y., Shioi, T., Iwasaki, A., Matsushima, K. and Sasayama, S. (1998) Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells. Arterioscler Thromb Vase Biol 18, 894–901CrossRefGoogle Scholar
  101. 101.
    Ranieri, V.M., Giunta, F., Suter, P.M., and Slutsky, A.S. (2000) Mechanical ventilation as a mediator of multisystem organ failure in acute respiratory distress syndrome. JAMA 284, 43–44PubMedCrossRefGoogle Scholar
  102. 102.
    Kuninaka, S., Yano, T., Yokoyama, H., Fukuyama, Y., Terazaki, Y., Uehara, T., Kanematsu, T., Asoh, H., and Ichinose, Y. (2000) Direct influences of proinflammatory cytokines (IL-1 beta, TNF-alpha, IL-6) on the proliferation and cell-surface antigen expression of cancer cells. Cytokine 12, 8–11PubMedCrossRefGoogle Scholar
  103. 103.
    Akira, S., Hirano, T., Taga, T., and Kishimoto, T. (1990) Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J 4, 2860–2867PubMedGoogle Scholar
  104. 104.
    Villavicencio, R.T., Liu, S., Kibbe, M.R., Williams, D.L., Ganster, R.W., Dyer, K.F., Tweardy, D.J., Billiar, T.R., and Pitt, B.R. (2000) Induced nitric oxide inhibits IL-6-induced stat3 activation and type II acute phase mRNA expression. Shock 13, 441–445PubMedCrossRefGoogle Scholar
  105. 105.
    Xing, Z., Gauldie, J., Cox, G., Baumann, H., Jordana, M., Lei, X.F., and Achong, M.K. (1998) IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 101, 311–320PubMedCrossRefGoogle Scholar
  106. 106.
    Bonfield, T.L., Konstan, M.W., Burfeind, P., Panuska, J.R., Hilliard, J.B., and Berger, M. (1995) Normal bronchial epithelial cells constitutively produce the anti-inflammatory cytokine interleukin-10, which is downregulated in cystic fibrosis. Am J Respir Cell Mol Biol 13, 257–261PubMedGoogle Scholar
  107. 107.
    Wanidworanun, C., and Strober. W. (1993) Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis. J Immunol 151, 6853–6861PubMedGoogle Scholar
  108. 108.
    Friedman, G., Jankowski, S., Marchant, A., Goldman, M., Kahn, R.J., and Vincent, J.L. (1997) Blood interleukin 10 levels parallel the severity of septic shock. J Crit Care 12, 183–187PubMedCrossRefGoogle Scholar
  109. 109.
    Donnelly, S.C., Strieter, R.M., Reid, P.T., Kunkel, S.L., Burdick, M.D., Armstrong, I., Mackenzie, A., and Haslett, C. (1996) The association between mortality rates and decreased concentrations of interleukin-10 and interleukin-1 receptor antagonist in the lung fluids of patients with the adult respiratory distress syndrome. Ann Intern Med 125, 191–196PubMedGoogle Scholar
  110. 110.
    Gazzinelli, R.T., Oswald, I.P., James, S.L., and Sher, A. (1992) IL-10 inhibits parasite killing and nitrogen oxide production by IFN- gamma-activated macrophages. J Immunol 148, 1792–1796PubMedGoogle Scholar
  111. 111.
    Lo, C.J., Fu, M., and Cryer, H.G. (1998) Interleukin 10 inhibits alveolar macrophage production of inflammatory mediators involved in adult respiratory distress syndrome. J Surg Res 79, 179–184PubMedCrossRefGoogle Scholar
  112. 112.
    Xing, Z., Ohkawara, Y., Jordana, M., Graham, F.L, and Gauldie, J. (1997) Adenoviral vector-mediated interleukin-10 expression in vivo: intramuscular gene transfer inhibits cytokine responses in endotoxemia. Gene Ther 4, 140–149PubMedCrossRefGoogle Scholar
  113. 113.
    Esmon, C.T., Taylor, F.B. Jr., and Snow, T. (1991) Inflammation and Coagulation: linked processes potentially regulated through a common pathway mediated by protein C. Thromb Haemostasis 66, 160–165Google Scholar
  114. 114.
    Chan, A.K., Baranowski, B., Berry, L., Liu, M., Rafii, B., Post, M., O’Brodovich, H., Monagle, P., and Andrew, M. (1998) Influence of mechanical stretch on thrombin regulation by fetal mixed lung cells. Am J Respir Cell Mol Biol 19, 419–425PubMedGoogle Scholar
  115. 115.
    Ruwhof, C., and van der, L.A. (2000) Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc Res 47, 23–37PubMedCrossRefGoogle Scholar
  116. 116.
    Cattaruzza, M., Dimigen, C., Ehrenreich, H., and Hecker, M. (2000) Stretch-induced endothelin B receptor-mediated apoptosis in vascular smooth muscle cells. FASEB J 14, 991–998PubMedGoogle Scholar
  117. 117.
    Behnia, R., Molteni, A., Waters, C.M., Panos, R.J., Ward, W.F., Schnaper, H.W., and TS’Ao, C.H. (1996) Early markers of ventilator-induced lung injury in rats. Ann Clin Lab Sci 26, 437–450PubMedGoogle Scholar
  118. 118.
    Simma, B., Gulberg, V., Schobel, P., Trawoger, R., Ulmer, H., Gerbes, A.L., and Putz, G. (2000) High-frequency oscillatory ventilation does not decrease endothelin release in lung-lavaged rabbits. Scand J Clin Lab Invest 60, 213–220PubMedCrossRefGoogle Scholar
  119. 119.
    Bernard, G., Vincent, J., Laterre, P., LaRosa, S., Dhainaut, J., Lopes-Rodriguez, A., Steingrub, J.S., Garber, G.E., Helterbrand, J.D., Ely, E.W., and Fisher, C.J. (2001) Efficacy and safety of recombinant human activated protein c for severe sepsis. N Engl J Med 344, 699–709PubMedCrossRefGoogle Scholar
  120. 120.
    White, B., Schmidt, M., Murphy, C., Livingstone, W., O’Toole, D., Lawler, M., O’Neill, L., Kelleher, D., Schwarz, H.P., and Smith, O.P. (2000) Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha) production in the THP-1 monocytic cell line. Br J Haematol 110, 130–134PubMedCrossRefGoogle Scholar
  121. 121.
    Esmon, C.T. (1987) The regulation of natural anticoagulant pathways. Science 235, 1348–1352PubMedCrossRefGoogle Scholar
  122. 122.
    Uchiba, M., Okajima, K., Murakami, K., Johno, M., Okabe, H., and Takatsuki, K. (1996) Recombinant thrombomodulin prevents endotoxin-induced lung injury in rats by inhibiting leukocyte activation. Am J Physiol 271, L470–L475PubMedGoogle Scholar
  123. 123.
    Grinnell, B.W., Hermann, R.B., and Yan, S.B. (1994) Human protein C inhibits selectin-mediated cell adhesion: role of unique fucosylated oligosaccharide. Glycobiology 4, 221–225PubMedCrossRefGoogle Scholar
  124. 124.
    Bevilacqua, M.P., Stengelin, S., Gimbrone, M.A, and Seed, B. (1989) Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243, 1160–1165PubMedCrossRefGoogle Scholar
  125. 125.
    Kuroki, Y., Tsutahara, S., Shijubo, N., Takahashi, H., Shiratori, M., Hattori, A., Honda, Y., Abe, S., and Akino, T. (1993) Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis. Am Rev Respir Dis 147, 723–729.PubMedGoogle Scholar
  126. 126.
    Chida, S., Phelps, D.S., Soll, R.F., and Taeusch, H.W. (1991) Surfactant proteins and anti-surfactant antibodies in sera from infants with respiratory distress syndrome with and without surfactant treatment. Pediatrics 88, 84–89PubMedGoogle Scholar
  127. 127.
    Honda, Y., Kuroki, Y., Matsuura, E. Nagae, H., Takahashi, H., Akino, T., and Abe, S. (1995) Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids. Am J Respir Crit Care Med 152, 1860–1866PubMedGoogle Scholar
  128. 128.
    Veldhuizen, R.A., Tremblay, L.N., Govindarajan, A., van Rozendaal, B.A., Haagsman, H.P., and Slutsky, A.S. (2000) Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung. Crit Care Med 28, 1545–2551Google Scholar
  129. 129.
    Verbrugge, S.J., Vazquez, D.A., Gommers, D., Neggers, S.J,, Sorm, V., Bohm, S.H., and Lachmann, B. (1998) Exogenous surfactant preserves lung function and reduces alveolar Evans blue dye influx in a rat model of ventilation-induced lung injury. Anesthesiology 89, 467–474PubMedCrossRefGoogle Scholar
  130. 130.
    Verbrugge, S.J., Bohm, S.H., Gommers, D., Zimmerman, L.J., and Lachmann, B. (1998) Surfactant impairment after mechanical ventilation with large alveolar surface area changes and effects of positive end-expiratory pressure. Br J Anaesth 80, 360–364PubMedCrossRefGoogle Scholar
  131. 131.
    Taskar, V., John, J., Evander, E., Robertson, B., and Jonson, B. (1997) Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion. Am J Respir Crit Care Med 155, 313–320PubMedGoogle Scholar
  132. 132.
    Rose, F., Zwick, K., Ghofrani, H.A., Sibelius, U., Seeger, W., Walmrath, D., and Grimminger, F. (1999) Prostacyclin enhances stretch-induced surfactant secretion in alveolar epithelial type II cells. Am J Respir Crit Care Med 160, 846–851PubMedGoogle Scholar
  133. 133.
    Rose, F., Kurth-Landwehr, C., Sibelius, U., Reuner, K.H., Aktories, K., Seeger, W., and Grimminger, F. (1999) Role of actin depolymerization in the surfactant secretory response of alveolar epithelial type II cells. Am J Respir Crit Care Med 159, 206–212PubMedGoogle Scholar
  134. 134.
    Floros, J., and Karinch, A.M. (1995) Human SP-A: then and now. Am J Physiol 268, L162–L165PubMedGoogle Scholar
  135. 135.
    Wright, J.R. (1997) Immunomodulatory functions of surfactant. Physiol Rev 77, 931–962PubMedGoogle Scholar
  136. 136.
    LeVine, A.M., Kurak, K.E., Bruno, M.D., Stark, J.M., Whitsett, J.A., and Korfhagen. T.R. (1998) Surfactant protein-A-deficient mice are susceptible to Pseudomonas aeruginosa infection. Am J Respir Cell Mol Biol 19, 700–708PubMedGoogle Scholar
  137. 137.
    Cochrane, C.G., and Revak, S.D. (1991) Pulmonary surfactant protein B (SP-B): structure-function relationships. Science 254, 566–568PubMedCrossRefGoogle Scholar
  138. 138.
    Whitsett, J.A., Nogee, L.M., Weaver, T.E., and Horowitz, A.D. (1995) Human surfactant protein B: structure, function, regulation, and genetic disease. Physiol Rev 75, 749–757PubMedGoogle Scholar
  139. 139.
    Arias-Diaz, J., Garcia-Verdugo, I., Casals, C., Sanchez-Rico, N., Vara, E., and Balibrea, J.L. (2000) Effect of surfactant protein A (SP-A) on the production of cytokines by human pulmonary macrophages. Shock 14, 300–306PubMedCrossRefGoogle Scholar
  140. 140.
    Chandel, N., and Sznajder, J. (2000) Stretching the lung and programmed cell death. Am J of Physiol Lung Cell Mol Physiol 279, L1003-L1004Google Scholar
  141. 141.
    Edwards, Y., Sutherland, L., and Murray, A. (2000) NO protects alveolar type II cells from stretch-induced apoptosis. A novel role for macrophages in the lung. Am J Physiol Lung Cell Mol Physiol 279, L1236–L1242PubMedGoogle Scholar
  142. 142.
    Davis, D.W., Weidner, D.A., Holian, A., and McConkey, D.J. (2000) Nitric oxide-dependent activation of p53 suppresses bleomycin-induced apoptosis in the lung. J Exp Med 192, 857–869PubMedCrossRefGoogle Scholar
  143. 143.
    Artlich, A., Adding, C., Agvald, P., Persson, M.G., Lonnqvist, P.A., and Gustafsson, L.E. (1999) Exhaled nitric oxide increases during high frequency oscillatory ventilation in rabbits. Exp Physiol 84, 959–969PubMedCrossRefGoogle Scholar
  144. 144.
    Bannenberg, G.L., and Gustafsson, L.E. (1997) Stretch-induced stimulation of lower airway nitric oxide formation in the guinea-pig: inhibition by gadolinium chloride. Pharmacol Toxicol 81, 13–18PubMedCrossRefGoogle Scholar
  145. 145.
    Ashino, Y., Ying, X., Dobbs, L.G., and Bhattacharya, J. (2000) [Ca(2+)](i) oscillations regulate type II cell exocytosis in the pulmonary alveolus. Am J Physiol Lung Cell Mol Physiol 279, L5–13PubMedGoogle Scholar
  146. 146.
    Kim, Y.M., Bombeck, C.A., and Billiar, T.R. (1999) Nitric oxide as a bifunctional regulator of apoptosis. Circ Res 84, 253–256PubMedCrossRefGoogle Scholar
  147. 147.
    Tanaka, Y., Kanai, Y., Okada, Y., Nonaka, S., Takeda, S., Harada, A., and Hirokawa, N. (1998) Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria. Cell 93, 1147–1158PubMedCrossRefGoogle Scholar
  148. 148.
    Downey, G.P., Dong, Q., Kruger, J., Dedhar, S., and Cherapanov, V. (1999) Regulation of neutrophil activation in acute lung injury. Chest 116, 46S–54SGoogle Scholar
  149. 149.
    Hamilton, P.P., Onayemi, A., Smyth, J.A., Gillan, J.E., Cutz, E., Froese, A.B., Bryan, A.C. (1983) Comparison of conventional and high-frequency ventilation: oxygenation and lung pathology. J Appl Physiol 55, 131–138PubMedGoogle Scholar
  150. 150.
    Zhang, F.X., Kirschning, C.J., Mancinelli, R., Xu, X.P., Jin, Y., Faure, E., Mantovani, A., Rothe, M., Muzio, M., and Arditi, M. (1999) Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J Biol Chem 274, 7611–7614PubMedCrossRefGoogle Scholar
  151. 151.
    Stenmark, K.R., and Mecham, R.P. (1997) Cellular and molecular mechanisms of pulmonary vascular remodeling. Annu Rev Physiol 59, 89–144PubMedCrossRefGoogle Scholar
  152. 152.
    Davies, P.F. (1995) Flow-mediated endothelial mechanotransduction. Physiol Rev 75. 519–560PubMedGoogle Scholar
  153. 153.
    Zimmerman, G.A., Albertine, K.H., Carveth, H.J., Gill, E.A., Grissom, C.K., Hoidal, J.R., Imaizumi, T., Maloney, C.G., McIntyre, T.M., Michael, J.R., Orme, J.F., Prescott, S.M., and Topham, M.S. (1999) Endothelial activation in ARDS. Chest 116, 18S–24SPubMedCrossRefGoogle Scholar
  154. 154.
    Beck, G.C., Yard, B.A., Breedijk, A.J., van Ackern, K., and Van Der Woude, F.J. (1999) Release of CXC-chemokines by human lung microvascular endothelial cells (LMVEC) compared with macrovascular umbilical vein endothelial cells. Clin Exp Immunol 118, 298–303PubMedCrossRefGoogle Scholar
  155. 155.
    Dunn, I., and Pugin, J. (1999) Mechanical ventilation of various human lung cells in vitro: identification of the macrophage as the main producer of inflammatory mediators. Chest 116, 95S–97SPubMedCrossRefGoogle Scholar
  156. 156.
    Pugin, J., Verghese, G., Widmer, M.C., and Matthay, M.A. (1999) The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome. Crit Care Med 27, 304–312PubMedCrossRefGoogle Scholar
  157. 157.
    Tremblay, L., Miatto, D., Hamid, Q., and Slutsky, A.S. (1997) Changes in cytokine expression secondary to injurious mechanical ventilation strategies in an ex vivo lung model. Intensive Care Med 23, S3CrossRefGoogle Scholar
  158. 158.
    McRitchie, D.I., Isowa, N., Edelson, J.D., Xavier, A.M., Cai, L., Man, H.Y., Wang, Y.T., Keshavjee, S.H., Slutsky, A.S., and Liu, M. (2000) Production of tumour necrosis factor alpha by primary cultured rat alveolar epithelial cells. Cytokine 12, 644–654PubMedCrossRefGoogle Scholar
  159. 159.
    Standiford, T.J., Kunkel, S.L., Basha, M.A., Chensue, S.W., Lynch, J.P., III, Toews, G.B., Westwick, J., and Strieter, R.M. (1990) Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. J Clin Invest 86, 1945–1953PubMedCrossRefGoogle Scholar
  160. 160.
    Vlahakis, N.E., Schroeder, M.A., Limper, A.H., and Hubmayr, R.D. (1999) Stretch induces cytokine release by alveolar epithelial cells in vitro. Am J Physiol 277, L167–L173PubMedGoogle Scholar
  161. 161.
    Tsuda, A., Stringer, B.K., Mijailovich, S.M., Rogers, R.A., Hamada, K., and Gray, M.L. (1999) Alveolar cell stretching in the presence of fibrous particles induces interleukin-8 responses. Am J Respir Cell Mol Biol 21, 455–462PubMedGoogle Scholar
  162. 162.
    Xavier, A.M., Isowa, N., Cai, L., Dziak, E., Opas, M., McRitchie, D.I., Slutsky, A.S., Keshavjee, S.H., and Liu, M. (1999) Tumor necrosis factor-alpha mediates lipopoly-saccharide-induced macrophage inflammatory protein-2 release from alveolar epithelial cells. Autoregulation in host defense. Am J Respir Cell Mol Biol 21, 510–520PubMedGoogle Scholar
  163. 163.
    West, J.B. (2000) Cellular Response to Mechanical Stress: Pulmonary Capillary Stress Failure. J Appl Physiol 89, 2483–2489PubMedGoogle Scholar
  164. 164.
    Savla, U., Appel, H.J. Sporn, P.H., and Waters, C.M. (2001) Prostaglandin E(2) regulates wound closure in airway epithelium. Am J Physiol Lung Cell Mol Physiol 280, L421–L431PubMedGoogle Scholar
  165. 165.
    Waters, C.M., and Savla, U. (1999) Keratinocyte growth factor accelerates wound closure in airway epithelium during cyclic mechanical strain. J Cell Physiol 181, 424–432PubMedCrossRefGoogle Scholar
  166. 166.
    Maron, M.B., Fu, Z., Mathieu-Costello, O., and West, J.B. (2001) Effect of high transcapillary pressures on capillary ultrastructure and permeability coefficients in dog lung. J Appl Physiol 90, 638–648PubMedGoogle Scholar
  167. 167.
    Nahum, A., Hoyt, J., Schmitz, L., Moody, J., Shapiro, R., and Marini, J.J. (1997) Effect of mechanical ventilation strategy on dissemination of intratracheally instilled Escherichia coli in dogs. Crit Care Med 25, 1733–1743PubMedCrossRefGoogle Scholar
  168. 168.
    Murphy, D.B., Cregg, N., Tremblay, L., Engelberts, D., Laffey, J.G., Slutsky, A.S., Romaschin, A, and Kavanagh, B.P. (2000) Adverse ventilatory strategy causes pulmonary-to-systemic translocation of endotoxin. Am J Respir Crit Care Med 162, 27–33PubMedGoogle Scholar
  169. 169.
    Savel, R.H., Yao, E.C., and Gropper, M.A. (2001) Protective effects of low tidal volume ventilation in a rabbit model of Pseudomonas aeruginosa-induced acute lung injury. Crit Care Med 29, 392–398PubMedCrossRefGoogle Scholar
  170. 170.
    Muscedere, J.G., Mullen, J.B., Gan, K., and Slutsky, A.S. (1994) Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 149, 1327–1334PubMedGoogle Scholar
  171. 171.
    Tutor, J.D., Mason, C.M., Dobard, E., Beckerman, R.C., Summer, W.R., and Nelson, S. (1994) Loss of compartmentalization of alveolar tumor necrosis factor after lung injury. Am J Respir Crit Care Med 149, 1107–1111PubMedGoogle Scholar
  172. 172.
    Debs, R.J., Fuchs, H.J., Philip, R., Montgomery, A.B., Brunette, E.N., Liggitt, D., Patton, J.S., and Shellito, J.E. (1988) Lung-specific delivery of cytokines induces sustained pulmonary and systemic immunomodulation in rats. J Immunol 140, 3482–3488PubMedGoogle Scholar
  173. 173.
    Wrigge, H., Zinserling, J., Stuber, F., von Spiegel, T., Hering, R., Wetegrove, S., Hoeft, A., and Putensen, C. (2000) Effects of mechanical ventilation on release of cytokines into systemic circulation in patients with normal pulmonary function. Anesthesiology 93, 1413–1417PubMedCrossRefGoogle Scholar
  174. 174.
    Mira, J.P., Cariou, A., Grall, F., Delclaux, C., Losser, M.R., Heshmati, F., Cheval, C., Monchi, M., Teboul, J.L., Riche, F., Leleu, G., Arbibe, L., Mignon, A., Delpech, M., and Dhainaut, J.F. (1999) Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. JAMA 282, 561–568PubMedCrossRefGoogle Scholar
  175. 175.
    Arbour, N.C., Lorenz, E., Schutte, B.C., Zabner, J., Kline, J.N., Jones, M., Frees, K., Watt, J.L., and Schwartz, D.A. (2000) TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 25, 187–191PubMedCrossRefGoogle Scholar
  176. 176.
    Slutsky, A.S. (2001) Basic Science in Ventilator-induced Lung Injury. Implications for the bedside. Am J Respir Crit Care Med 163, 599–600PubMedGoogle Scholar
  177. 177.
    Imai, Y., Kawano, T., Iwamoto, S., Nakagawa, S., Takata, M., Miyasaka, K. (1999) Intratracheal anti-tumor necrosis factor-alpha antibody attenuates ventilator-induced lung injury in rabbits. J Appl Physiol 87, 510–515PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Claudia C. dos Santos
    • 1
    • 2
    • 3
  • Mingyao Liu
    • 1
    • 2
    • 3
  • Arthur S. Slutsky
    • 1
    • 2
    • 3
  1. 1.Inter-Departmental Division of Critical CareUniversity of TorontoCanada
  2. 2.Thoracic Surgery Research LaboratoryUniversity Health Network, Toronto General HospitalCanada
  3. 3.Department of Critical Care MedicineSt. Michael’s HospitalTorontoCanada

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