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Superoxide anion production by rat neutrophils at various stages of bleomycin-induced lung injury

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Abstract

This study investigated the level of activation of neutrophils isolated from rats at various stages of bleomycin-induced lung injury. Neutrophils were collected from blood and bronchoalveolar lavage (BAL) fluid and their superoxide anion (O p−f2 )-generating capacity measured in response to phorbol myristate acetate (PMA) and opsonized zymosan (OZ) stimulation. When stimulated with PMA, BAL neutrophils isolated from animals 3 days after bleomycin treatment had a significantly greater capacity to produce O p−f2 than BAL neutrophils from animals 7 days after bleomycin treatment. The O p−f2 levels of 7 day BAL neutrophils more closely resembled the resting levels obtained with circulating neutrophils from both control and bleomycin-treated animals. There were no differences observed in any of the neutrophils when stimulated with OZ. Myeloperoxidase levels were measured in plasma and BAL and found to be elevated only in plasma at 7 days after bleomycin. These data demonstrate that neutrophil activation does occur in this model and that the activation appears to be transient, in response to specific stimuli and compartmentalized between the lung and blood.

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References

  1. Adamson IYR, Bowden DH (1974) The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol 77:185–198

    Google Scholar 

  2. Baldwin SR, Grum CM, Boxer LA, Simon RH, Ketan LH, Deuvall LJ (1986) Oxidant activity in expired breath of patients with adult respiratory distress syndrome. Lancet 1(8471):11–13

    Google Scholar 

  3. Berend N, Feldsien D, Cederbaums D, Cherniack RM (1985) Structure-function correlation of early stages of lung injury induced by intratracheal bleomycin in the rabbit. Am Rev Respir Dis 132:582–589

    Google Scholar 

  4. Boyd MR, Catigrani GL, Sasame HA, Mitchell JR, Stiko AW (1979) Acute pulmonary injury in rats by nitrofurantoin and modification by vitamin E, dietary fat, and oxygen. Am Rev Respir Dis 120:93–99

    Google Scholar 

  5. Brown EJ (1989) The interaction of small oligomers of complement 3B (C3B) with phagocytes. High affinity binding and phorbal ester induced internalization by polymorphonuclear leukocytes. J Biol Chem 264:6196–6201

    Google Scholar 

  6. Carp H, Miller F, Hoidal JR, Janoff A (1982) Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity. Proc Natl Acad Sci USA 79:2041–2045

    Google Scholar 

  7. Chandler DB, Barton JC, Briggs DD, Butler TW, Kennedy JI, Grizzle WE, Fulmer JD (1988) Effect of iron deficiency on bleomycin-induced lung fibrosis in the hamster. Am Rev Respir Dis 137:85–89

    Google Scholar 

  8. Clark JG, Kuhn C (1982) Bleomycin-induced pulmonary fibrosis in hamsters: effect of neutrophil depletion on lung collagen synthesis. Am Rev Respir Dis 126:737–739

    Google Scholar 

  9. Cohen HJ, Chovaniec ME (1978) Superoxide generated by digitoxin in stimulated guinea pig granulocytes. J Clin Invest 61:1081–1087

    Google Scholar 

  10. Cooper JA, White DA, Mathay RA (1986) Drug-induced pulmonary disease. Am Rev Respir Dis 133:321–340

    Google Scholar 

  11. Eiermann GJ, Dickey BF, Thrall RS (1983) Polymorphonuclear leukocyte participation in acute oleic acid-induced lung injury. Am Rev Respir Dis 128:845–850

    Google Scholar 

  12. Fantone JC, Ward PA (1982) Role of oxygen-derived free radicals and metabolites in leukocyte dependent inflammatory reactions. Am J Pathol 107:397–418

    Google Scholar 

  13. Fisher AB (1980) Oxygen therapy: side effects and toxicity. Am Rev Respir Dis 122:61–69

    Google Scholar 

  14. Fleischman RW, Baker JR, Thompson GR, Schaeppi UH, Illievski VR, Cooney DA, Davis RD (1971) Bleomycin induced interstitial pneumonia in dogs. Thorax 26:675–682

    Google Scholar 

  15. Fowler AA, Hyers TM, Fisher BJ, Bechard DE, Centor RM, Webster RD (1987) The adult respiratory distress syndrome. Cell populations and soluble mediators in the air spaces of patients at high risk. Am Rev Respir Dis 136:1225–1231

    Google Scholar 

  16. Freeman BA, Crapo JD (1981) Hyperoxia increases oxygen radical production in rat lung and lung mitochondria. J Biol Chem 256:10986–10992

    Google Scholar 

  17. Goldblum SE, Wu KM, Jay M (1985) Lung myeloperoxide as a measure of pulmonary leukostatis in rabbits. J Appl Physiol 59:1978–1985

    Google Scholar 

  18. Gross NJ (1977) Pulmonary effects of radiation therapy. Ann Intern Med 86:81–92

    Google Scholar 

  19. Guthrie LA, McPhail LC, Henson PM, Johnston RB (1984) Priming of neutrophils for enhanced release of oxygen metabolites by bacterial lipopolysaccharide. Evidence for increased activity of the superoxide producing enzyme. J Exp Med 160:1656–1661

    Google Scholar 

  20. Henson PM, Zanolin B, Schwartznan RDA, Hong SR (1978) Intracellular control of human neutrophil secretion I. C5a-induced stimulus-specific demonstration and the effectof cytochalasin B. J Immunol 121:851–855

    Google Scholar 

  21. Hoover RL, Robinson JM, Karnovsky MJ (1987) Adhesion of polymorphonuclear leukocytes to endothelium enhances the efficiency of detoxification of oxygen free radicals. Am J Pathol 126:258–268

    Google Scholar 

  22. Jenkinson SG, Duncan CA, Lawrence RA, Collins JF (1987) Lack of enhancement of bleomycin lung injury in vitamin E-deficient rats. J Crit Care 2:264–269

    Google Scholar 

  23. Johnson KJ, Ward PA (1982) Acute and progressive lung injury after contact with phorbol myristate acetate. Am J Pathos 107:29–35

    Google Scholar 

  24. Klebanoff SJ (1980) Oxygen metabolism and toxic properties of phagocytes. Ann Intern Med 93:480–489

    Google Scholar 

  25. Martin WJ, Gadek JE, Hunnighake GW, Crystal RG (1981) Oxidant injury of lung parenchymal cells. J Clin Invest 68:1277–1288

    Google Scholar 

  26. Massey V (1956) The microestimation of succinate and the extinction coefficient of cytochrome C. Biochim Biophys Acta 34:255–256

    Google Scholar 

  27. McCord JM, Fridovich I (1978) The biology and pathology of oxygen radicals. Ann Intern Med 89:122–127

    Google Scholar 

  28. McCullough B, Collins JF, Johanson WG, Grover FL (1978) Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons. J Clin Invest 61:79–88

    Google Scholar 

  29. Mustafa MG, Tierney DF (1978) Biochemical and metabolic changes in the lung with oxygen, ozone and nitrogen dioxide toxicity. Am Rev Respir Dis 118:1061–1088

    Google Scholar 

  30. Oberley LW, Buettner GR (1979) The production of hydroxyl radical by bleomycin and iron (II). FEBS Lett 97:47–49

    Google Scholar 

  31. O'Flaherty JT, Redman JF, Jacobson DP, Rossi AG (1990) Stimulation and priming of protein kinase C translocation by a Ca transient independent mechanism. Studies in human neutrophils challenged with platelet activating factor and other receptor agonists. J Biol Chem 265:21619–21623

    Google Scholar 

  32. Rister M, Baehner RL (1976) The alteration of superoxide dismutase, catalase, glutathione peroxidase and NADPH cytochrome C reductase in guinea pig polymorphonuclear leukocytes and alveolar macrophages during hyperoxia. J Clin Invest 58:1174–1184

    Google Scholar 

  33. Shasby DM, Vanbenthuysen KM, Tate RM, Shasby SS, McMurtry I, Repine JE (1982) Granulocytes mediate acute edematous lung injury in rabbits and in isolated rabbit lungs perfused with phorbol myristate acetate: role of oxygen radicals. Am Rev Respir Dis 125:443–447

    Google Scholar 

  34. Snider GL, Bartolome RL, Goldstein RH, O'Brien JJ, Lucey EC (1978) Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin. Am Rev Respir Dis 117:289–297

    Google Scholar 

  35. Thrall RS, McCormick JR, Jack RM, McReynolds RA, Ward PA (1979) Bleomycin-induced pulmonary fibrosis in the rat. Am J Pathol 95:117–130

    Google Scholar 

  36. Thrall RS, Phan SH, McCormick JR, Ward PA (1981) The development of bleomycin-induced pulmonary fibrosis in neutrophil-depleted and complement-depleted rats. Am J Pathol 105:76–81

    Google Scholar 

  37. Thrall RS, Barton RW, D'Amato DA, Sulavik SB (1982) Differential cellular analysis of bronchoalveolar lavage fluid obtained at various stages during the development of bleomycin-induced pulmonary fibrosis in the rat. Am Rev Respir Dis 120:488–492

    Google Scholar 

  38. Vercellotti GM, Yin HQ, Gustafson KS, Nelson RD, Jacob HS (1988) Platelet activating actor primes neutrophil responses to agonists: role in promoting neutrophil mediated endothelial damage. Blood 71:1100–1107

    Google Scholar 

  39. Watts FL, Oliver BL, Johnson GM, Thrall RS (1990) Superoxide production by rat neutrophils in the oleic acid model of lung injury. Free Radical Biol Med 9:327–332

    Google Scholar 

  40. Webster RO, Henson PM (1978) Rapid measurement of neutrophil exocytosis. Inflammation 3:129–135

    Google Scholar 

  41. Weiland JD, Davis WB, Holder JF, Mohammed JR Jr, Dorinsky PM, Gadek JE (1986) Lung neutrophils in the adult respiratory distress syndrome, clinical and pathophysiologic significance. Am Rev Respir Dis 133:218–225

    Google Scholar 

  42. Zar J (1984) Biostatistical analysis. Prentice Hall, Inglewood, CA, pp 162–260

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Pulmonary Division, University of Connecticut Health Center, 06030, Farmington, CT, USA

    Elizabeth B. Tarnell, Bonnie L. Oliver & Roger S. Thrall

  2. Department of Pediatrics, University of Connecticut Health Center, 06030, Farmington, CT, USA

    George M. Johnson

  3. Department of Anesthesiology, University of Connecticut Health Center, 06030, Farmington, CT, USA

    Florence L. Watts

Authors
  1. Elizabeth B. Tarnell
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  2. Bonnie L. Oliver
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  3. George M. Johnson
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  4. Florence L. Watts
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  5. Roger S. Thrall
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Tarnell, E.B., Oliver, B.L., Johnson, G.M. et al. Superoxide anion production by rat neutrophils at various stages of bleomycin-induced lung injury. Lung 170, 41–50 (1992). https://doi.org/10.1007/BF00164754

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