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Endotoxemia and complement activation after severe burn injuries-effects on leukocytes, soluble selectins, and inflammatory cytokines

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Abstract

In this study we followed the development of an inflammatory response in a group of patients the first week after a burn injury. We detected elevated plasma endotoxin levels, on at least one occasion, in 6 of 8 patients. No endotoxin was detected in the two patients with the lowest total burned surface area (≤30%). We found evidence of complement activation as increased C3a levels, in parallel with a production of inflammatory cytokines (TNF-α, IL-6). The TNF-α levels increased significantly during the observation period, while the IL-6 levels were elevated already at admission, and remained so. Elevated levels of soluble E-selectin were detected, indicating endothelial cell activation. Despite the inflammatory response and a loss of inflammatory cells during the first days of the monitoring period, we found no evidence of cellular activation measured as increased expression of β2 integrin CD11b, nor increased plasma levels of soluble L-selectin.

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References

  1. Parker, M. M., andJ. E. Parillo. 1983. Septic shock. Hemodynamics and pathogenesis.JAMA 250:3324–3327.

    Google Scholar 

  2. Shapiro, L., andJ. A. Gelfand. 1993. Cytokines and sepsis: pathophysiology and therapy.New Horizons 1:13–22.

    Google Scholar 

  3. Sturk, A., S. J. H. Van Deventer, C. H. Wortel, J. H. M. Levels, J. W. ten Cate, H. R. Büller andG. T. B. Sanders. 1990. Detection and clinical relevance of human endotoxemia.Z. Med. Lab. Diagn. 31:147–158.

    Google Scholar 

  4. Lundahl, J., andJ. Hed. 1994. Differences in altered expression of L-selectin and Mac-1 in monocytes and neutrophils.Inflammation 18:67–76.

    Google Scholar 

  5. Jutila, M. A., L. Rott, E. L. Berg, andE. C. Butcher. 1989. Function and regulation of the neutrophil MEL-14 antigen in vivo: comparison with LFA-1 and MAC-1.J. Immunol. 143:3318–3324.

    Google Scholar 

  6. Smith, C. W., T. K. Kishimoto, O. Abbass, B. Hughes, R. Rothlein, L. V. McIntire, E. Butcher, andD. C. Anderson. 1991. Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro.J. Clin. Invest. 87:609–618.

    Google Scholar 

  7. von Andrian, U. H., J. D. Chambers, L. M. McEvoy, R. F. Bargatze, K. E. Arfors, andE. C. Butcher. 1991. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte β2 integrins in vivo.Proc. Natl. Acad. Sci. USA 88:7538–7542.

    Google Scholar 

  8. Zimmerman, G. A., S. M. Prescott, andT. M. McIntyre. 1992. Endothelial cell interactions with granulocytes: tethering and signaling molecules.Immunol. Today 13:93–100.

    Google Scholar 

  9. Sengeløv, H., L. Kjeldsen, M. S. Diamond, T. A. Springer, andN. Borregaard. 1993. Subcellular localization and dynamics of Mac-1 (αm/β2) in human neutrophils.J. Clin. Invest. 92:1467–1476.

    Google Scholar 

  10. Kishimoto, T. K., M. A. Jutila, E. L. Berg, andE. C. Butcher. 1989. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors.Science 245:1238–1241.

    Google Scholar 

  11. Smith, C. W., S. D. Marlin, R. Rothlein, M. B. Lawrence, L. V. McIntire, andD. C. Anderson. 1988. Role of ICAM-1 in the adherence of human neutrophils to human endothelial cells in vitro. In Leukocyte Adhesion Molecules. Springer, T. A., Anderson, D. C., Rosenthal, A. S., and Rothlein, R. (Eds.) Springer-Verlag, New York, pp. 170–189.

    Google Scholar 

  12. Diamond, M. S., D. E. Staunton, A. R. de Fougerolles, S. A. Stacker, J. Garcia-Aguilar, M. L. Hibbs, andT. A. Springer. 1990. ICAM-1 (CD54): a counter-receptor for MAC-1 (CD11b/CD18).J. Cell Biol. 111:3129–3139.

    Google Scholar 

  13. Pober, J. S., M. A. Gimbrone, Jr., L. A. Lapierre, D. L. Mendrick, W. Fiers, R. Rothlein, andT. A. Springer. 1986. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon.J. Immunol. 137:1893–1896.

    Google Scholar 

  14. Bevilacqua, M. P., J. S. Pober, D. L. Mendrick, R. S. Cotran, andM. A. Gimbrone, Jr. 1987. Identification of an inducible endothelial-leukocyte adhesion molecule.Proc. Natl. Acad. Sci. USA 84:9238–9242.

    Google Scholar 

  15. Staunton, D. E., S. D. Marlin, C. Stratowa, M. L. Dustin, andT. A. Springer. 1988. Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families.Cell 52:925–933.

    Google Scholar 

  16. Bevilacqua, M. P., andR. M. Nelson. 1993. Selectins.J. Clin. Invest. 91:379–387.

    Google Scholar 

  17. Wright, S. D., R. A. Ramos, P. S. Tobias, R. J. Ulevitch, andJ. C. Mathison. 1990. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein.Science 249:1431–1433.

    Google Scholar 

  18. Schumann, R. R., S. R. Leong, G. W. Flaggs, P. W. Gray, S. D. Wright, J. C. Mathison, P. S. Tobias, andR. J. Ulevitch. 1990. Structure and function of lipopolysaccharide binding protein.Science 249:1429–1431.

    Google Scholar 

  19. van der Poll, T., H. R. Büller, H. ten Cate, C. H. Wortel, K. A. Bauer, S. J. H. van Deventer, C. E. Hack, H. P. Sauerwein, R. D. Rosenberg andJ. W. ten Cate. 1990. Activation of coagulation after administration of tumor necrosis factor to normal subjects.N. Engl. J. Med. 322:1622–1627.

    Google Scholar 

  20. Fong, Y. K. J., Tracey, L. L. Moldawer, D. G. Hesse, K. B. Manogue, J. S. Kenney, A. T. Lee, G. C. Kuo, A. C. Allison, S. F. Lowry, andA. Cerami. 1989. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1β and interleukin 6 appearance during lethal bacteremia.J. Exp. Med. 170:1627–1633.

    Google Scholar 

  21. Beutler, B., andA. Cerami. 1987. Cachectin: more than a tumor necrosis factor.N. Engl. J. Med. 316:379–385.

    Google Scholar 

  22. Michie, H. R., andD. W. Wilmore. 1990. Sepsis and tumor necrosis factor-badfellows that cannot be ignored.Ann. Surg. 212:653–654.

    Google Scholar 

  23. Beutler, B. 1993. Endotoxin, tumor necrosis factor, and related mediators: new approaches to shock.New Horizons 1:3–12.

    Google Scholar 

  24. Fearon, D. T., andL. A. Collins. 1983. Increased expression of C3b receptors on polymorphonuclear leukocytes induced by chemotactic factors and by purification procedures.J. Immunol. 130:370–375.

    Google Scholar 

  25. Welch-Barker, J. 1988. An innovative lymphocyte preparation system for flow cytometry.Am. Clin. Lab. 7:32–37.

    Google Scholar 

  26. vanDeventer, S. J. H. 1988. Endotoxins in the pathogenesis of gram-negative septicemia. Thesis. Amsterdam.

  27. Nilsson-Ekdahl, K., B. Nilsson, M. Pekna, andU. Nilsson. 1992. Generation of iC3a at the interface between blood and gas.Scand. J. Immunol. 35:85–91.

    Google Scholar 

  28. Winchurch, R. A., J. N. Thupari, andA. M. Munster. 1987. Endotoxemia in burn patients: levels of circulating endotoxins are related to burn size.Surgery 102:808–812.

    Google Scholar 

  29. Deitch, E. A., 1990. Intestinal permeability is increased in burn patients shortly after injury.Surgery 107:411–416.

    Google Scholar 

  30. Lawrence, J. C. 1983. Bacteriology and wound healing. InCadexomer Iodine, Fox, J. A. and Fischer, H. (Eds.), Schattauer, Stuttgart.

    Google Scholar 

  31. Wright, S. D., S. M. Levin, M. T. C. Jong, Z. Chad, andL. G. Kabbash, 1989. CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-Asp-containing peptides and a second site for bacterial lipopolysaccharide.J. Exp. Med. 169:175–183.

    Google Scholar 

  32. Craddock, Jr., C. G., S. Perry, L. E. Ventzke, andJ. S. Lawrence. 1960. Evaluation of marrow granulocytic reserves in normal and disease states.Blood 15:840–855.

    Google Scholar 

  33. Fiebig, E., K. Ley, andK. E. Arfors. 1991. Rapid leukocyte accumulation by “spontaneous” rolling and adhesion in the exteriorized rabbit mesentery.Int. J. Microcirc. Clin. Exp. 10:127–144.

    Google Scholar 

  34. Moore, Jr., F. D., andC. F. Davis. 1989. Monocyte activation after burns and endotoxemia.J. Surg. Res. 46:350–354.

    Google Scholar 

  35. Arnaout, M. A., R. M. Hakim, R. F. Todd III, N. Dana, andH. R. Colten. 1985. Increased expression of an adhesion-promoting surface glycoprotein in the granulocytopenia of hemodialysis.New Engl. J. Med. 312:457–462.

    Google Scholar 

  36. Philips, M. R., J. P. Buyon, R. Winchester, G. Weissman, andS. B. Abramson. 1988. Up-regulation of the iC3b receptor (CR3) is neither necessary nor sufficient to promote neutrophil aggregation.J. Clin. Invest. 82:495–501.

    Google Scholar 

  37. Vedder, N. B., andJ. M. Harlan. 1988. Increased surface expression of CD11b/CD18 (Mac-1) is not required for stimulated neutrophil adherence to cultured endothelium.J. Clin. Invest. 81:676–682.

    Google Scholar 

  38. Lo, S. K., P. A. Detmers, S. M. Levin, andS. D. Wright. 1989. Transient adhesion of neutrophils to endothelium.J. Exp. Med. 169:1779–1793.

    Google Scholar 

  39. Ljunghusen, O., S. Berg, J. Lundahl, H. Nettelblad, F. Sjögren, andO. Stendahl. 1995. Transient endotoxemia during wound revision causes leukocyte β2 integrin up regulation and cytokine release.Inflammation 19:457–468.

    Google Scholar 

  40. Gearing, A. J. H., andW. Newman, 1993. Circulation adhesion molecules in disease.Immunol. Today 14:506–512.

    Google Scholar 

  41. Jirik, F. R., T. J. Podor, T. Hirano, T. Kishimoto, D. J. Loskutoff, D. A. Carson, andM. Lotz. 1989. Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells.J. Immunol. 142:144–147.

    Google Scholar 

  42. Ueyama, M., I. Maruyama, M. Osame, andY. Sawada. 1992. Marked increase in plasma interleukin-6 in burn patients.J. Lab. Clin. Med. 120:693–698.

    Google Scholar 

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Ljunghusen, O., Lundahl, J., Nettelblad, H. et al. Endotoxemia and complement activation after severe burn injuries-effects on leukocytes, soluble selectins, and inflammatory cytokines. Inflammation 20, 229–241 (1996). https://doi.org/10.1007/BF01488201

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