A superoxide-activated chemotactic factor and its role in the inflammatory process
- 12 Downloads
Superoxide dismutase or derivatives thereof have been shown to be potent anti-inflammatory agents in several models of induced inflammation. In all cases, the anti-inflammatory effects included a marked suppression of the accumulation of inflammatory cells at the site of the potential lesion, suggesting a role for the superoxide radical in the chemotaxis process. The exposure of normal plasma to a source of superoxide in vitro resulted in the formation of a powerful chemotactic factor for human neutrophils. The factor is activated by reacting specifically with superoxide, and was found to consist of a complex of serum albumin and an unidentified lipid. The complex may be resolved and reconstituted. Both components are required for expression of biologic activity. The major mechanism for the anti-inflammatory activity of superoxide dismutase appears to be the prevention of the formation of this plasma-derived superoxide-dependent chemotactic factor.
KeywordsLipid Albumin Superoxide Serum Albumin Inflammatory Cell
Unable to display preview. Download preview PDF.
- A.J. Sbarra andM.L. Karnovsky,The Biochemical Basis of Phagocytosis. I. Metabolic Changes During the Ingestion of Particles by Polymorphonuclear Leukocytes, J. Biol. Chem.234, 1355–1362 (1969).Google Scholar
- R.B. Johnston, Jr., B.B. Keele, Jr., H.P. Misra, J.E. Lehmeyer, L.S. Webb, R.L. Baehner andK.V. Rajagopalan,The Role of Superoxide Anion Generation in Phagocytic Bacterial Activity. Studies with Normal and Chronic Granulomatous Disease Leukocytes, J. Clin. Invest.55, 1357–1372 (1975).PubMedGoogle Scholar
- K.B. Menander-Huber andW. Huber,Orgotein, the Drug Version of Bovine Cu−Zn Superoxide Dismutase. II. A Summary Account of Clinical Trials in Man and Animals, in:Superoxide and Superoxide Dismutases (Eds. A.M. Michelson, J.M. McCord and I. Fridovich; Academic Press, New York 1977), pp. 537–549.Google Scholar
- J.M. McCord andK. Wong,Phagocyte-Produced Free Radicals: Roles in Cytotoxicity and Inflammation, in:Oxygen Free Radicals and Tissue Damage (Ciba Found. Symp. 65) (Elsevier/Excerpta Medica/North Holland, Amsterdam 1979), pp. 343–360.Google Scholar
- J.M. McCord, S.H. Stokes andK. Wong,Superoxide Radical as a Phagocyte-Produced Chemical Mediator of Inflammation, in:Advances in Inflammation Research, vol. 1 (Eds. G. Weissmann et al.; Raven Press, New York 1979), pp. 273–280.Google Scholar
- J.M. McCord, J.A. Boyle, E.D. Day, Jr., L.J. Rizzolo andM.L. Salin,A Manganese-Containing Superoxide Dismutase from Human Liver, in:Superoxide and Superoxide Dismutases (Eds. A.M. Michelson, J.M. McCord and I. Fridovich; Academic Press, New York 1977), pp. 129–138.Google Scholar
- K. Vinegar, W. Schreiber andR. Hugo,Biphasic Development of Carrageenin Edema in Rats, J. Pharmac. exp. Ther.166, 96–103 (1969).Google Scholar