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. 1994 Dec;102(Suppl 10):57–60. doi: 10.1289/ehp.94102s1057

Neutrophil-generated free radicals: possible mechanisms of injury in adult respiratory distress syndrome.

J M McCord 1, B Gao 1, J Leff 1, S C Flores 1
PMCID: PMC1566997  PMID: 7705307

Abstract

The acute lung injury resulting from adult respiratory distress syndrome (ARDS) is thought to be largely mediated by activated neutrophils. Because activated neutrophils produce the superoxide radical, which is both bacterial and cytotoxic to host cells, this oxygen-derived free radical is likely responsible for at least part of the neutrophil-mediated lung injury. In a rat model of ARDS resulting from intratracheal instillation of interleukin-1, recombinant human manganous superoxide dismutase significantly decreased lung leak. One detrimental action of proteases released by adherent neutrophils may be the degradation of extracellular superoxide dismutase (ECSOD), which normally binds to the heparan sulfate on the surface the endothelium. We found that rabbit ECSOD incubated with either trypsin or activated neutrophils loses affinity for heparin. Furthermore, soluble ECSOD is elevated in the serum of patients with ARDS, consistent with this hypothesis.

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Selected References

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  1. Adachi T., Marklund S. L. Interactions between human extracellular superoxide dismutase C and sulfated polysaccharides. J Biol Chem. 1989 May 25;264(15):8537–8541. [PubMed] [Google Scholar]
  2. Bertrand Y. Oxygen-free radicals and lipid peroxidation in adult respiratory distress syndrome. Intensive Care Med. 1985;11(2):56–60. doi: 10.1007/BF00254774. [DOI] [PubMed] [Google Scholar]
  3. Cochrane C. G., Spragg R., Revak S. D. Pathogenesis of the adult respiratory distress syndrome. Evidence of oxidant activity in bronchoalveolar lavage fluid. J Clin Invest. 1983 Mar;71(3):754–761. doi: 10.1172/JCI110823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Crapo J. D., McCord J. M., Fridovich I. Preparation and assay of superoxide dismutases. Methods Enzymol. 1978;53:382–393. doi: 10.1016/s0076-6879(78)53044-9. [DOI] [PubMed] [Google Scholar]
  5. Hatori N., Sjöquist P. O., Marklund S. L., Rydén L. Effects of recombinant human extracellular-superoxide dismutase type C on myocardial infarct size in pigs. Free Radic Biol Med. 1992 Sep;13(3):221–230. doi: 10.1016/0891-5849(92)90018-c. [DOI] [PubMed] [Google Scholar]
  6. Karlsson K., Edlund A., Sandström J., Marklund S. L. Proteolytic modification of the heparin-binding affinity of extracellular superoxide dismutase. Biochem J. 1993 Mar 1;290(Pt 2):623–626. doi: 10.1042/bj2900623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Knox T. A., Hillyer C. D., Kaplan M. M., Berkman E. M. Mixed cryoglobulinemia responsive to interferon-alpha. Am J Med. 1991 Nov;91(5):554–555. doi: 10.1016/0002-9343(91)90196-5. [DOI] [PubMed] [Google Scholar]
  8. Marklund S. L. Extracellular superoxide dismutase and other superoxide dismutase isoenzymes in tissues from nine mammalian species. Biochem J. 1984 Sep 15;222(3):649–655. doi: 10.1042/bj2220649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Marklund S. L. Human copper-containing superoxide dismutase of high molecular weight. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7634–7638. doi: 10.1073/pnas.79.24.7634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Marklund S. L. Properties of extracellular superoxide dismutase from human lung. Biochem J. 1984 May 15;220(1):269–272. doi: 10.1042/bj2200269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McCord J. M., Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049–6055. [PubMed] [Google Scholar]
  12. Omar B. A., McCord J. M. Interstitial equilibration of superoxide dismutase correlates with its protective effect in the isolated rabbit heart. J Mol Cell Cardiol. 1991 Feb;23(2):149–159. doi: 10.1016/0022-2828(91)90102-r. [DOI] [PubMed] [Google Scholar]
  13. Repine J. E. Scientific perspectives on adult respiratory distress syndrome. Lancet. 1992 Feb 22;339(8791):466–469. doi: 10.1016/0140-6736(92)91067-i. [DOI] [PubMed] [Google Scholar]
  14. Salin M. L., McCord J. M. Free radicals and inflammation. Protection of phagocytosine leukocytes by superoxide dismutase. J Clin Invest. 1975 Nov;56(5):1319–1323. doi: 10.1172/JCI108208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sandström J., Carlsson L., Marklund S. L., Edlund T. The heparin-binding domain of extracellular superoxide dismutase C and formation of variants with reduced heparin affinity. J Biol Chem. 1992 Sep 5;267(25):18205–18209. [PubMed] [Google Scholar]
  16. Sznajder J. I., Fraiman A., Hall J. B., Sanders W., Schmidt G., Crawford G., Nahum A., Factor P., Wood L. D. Increased hydrogen peroxide in the expired breath of patients with acute hypoxemic respiratory failure. Chest. 1989 Sep;96(3):606–612. doi: 10.1378/chest.96.3.606. [DOI] [PubMed] [Google Scholar]
  17. Tate R. M., Repine J. E. Neutrophils and the adult respiratory distress syndrome. Am Rev Respir Dis. 1983 Sep;128(3):552–559. doi: 10.1164/arrd.1983.128.3.552. [DOI] [PubMed] [Google Scholar]

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