Role of O2- in neutrophil recruitment into sites of dermal and pulmonary vasculitis.
Using analogous models of acute dermal vasculitis and alveolitis in rats, we have examined the role of oxygen-derived metabolities in the tissue damage associated with neutrophil influx into sites of immune complex deposition. In the lung, as previously reported, catalase and deferoxamine are highly protective, while superoxide dismutase (SOD) has a transient protective effect. The xanthine oxidase inhibitors, allopurinol, and lodoxamide, are also protective. In the skin, neither catalase (which has been covalently linked to the antibody) nor deferoxamine is protective, suggesting that H2O2 and iron are not absolutely required for the development of dermal vasculitis. In the skin, SOD, as well as the inhibitors of xanthine oxidase, have protective effects. These data suggest that the neutrophil-mediated pathways of immune complex injury in the dermal and pulmonary microvascular compartments are fundamentally different. As a measurement of neutrophil accumulation, measurements of myeloperoxidase in tissue extracts have been employed. In both the lung and skin, the protective effects of SOD and the xanthine oxidase inhibitors are paralleled by reductions in neutrophil influx into sites of injury. In contrast, catalase and deferoxamine have no effect on neutrophil accumulation. These data suggest that vascular beds in rat skin and lung are fundamentally different with respect to mechanisms of acute immune complex mediated injury. The data also provide evidence that O2- contributes significantly to the accumulation of neutrophils.
Warren
J S
JS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Yabroff
K R
KR
Mandel
D M
DM
Johnson
K J
KJ
Ward
P A
PA
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D005609:Free Radicals; D008297:Male; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D014657:Vasculitis / Q000503:physiopathology*; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000503:physiopathology*
D000975:Antioxidants; D005609:Free Radicals; D000493:Allopurinol; D009195:Peroxidase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D010072:Oxamic Acid; D010100:Oxygen; C021702:lodoxamide ethyl