Evidence for a role of hydroxyl radical in immune-complex-induced vasculitis.
Previously it was shown that tissue injury occurring in acute immune-complex-induced vasculitis, which is complement and neutrophil-dependent, is significantly attenuated by the presence of catalase, suggesting the pathogenic role of H2O2 generated from activated neutrophils. We now show that significant protection is also afforded by pretreatment of animals with apolactoferrin , a naturally occurring chelator of iron. Iron-saturated lactoferrin is devoid of protective effects. Deferoxamine mesylate, a synthetic iron chelator, also has protective effects. Infusion of ionic iron, especially Fe(III), potentiates the tissue injury. Significant protection from tissue injury is also produced by treatment of rats with dimethyl sulfoxide, a potent hydroxyl radical scavenger. Morphologically, animals treated with these protective interventions show the influx of neutrophils into sites of immune complex deposition, but there is markedly attenuated edema, little or no hemorrhage, and little evidence of endothelial cell injury, in contrast to the findings in nonprotected animals. These data support the suggestion that immune-complex-induced injury may be linked to generation of H2O2 from activated neutrophils and the subsequent conversion of H2O2 to the hydroxyl radical.
D000818:Animals; D001059:Apoproteins / Q000627:therapeutic use; D001183:Arthus Reaction / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002712:Chlorides; D003676:Deferoxamine / Q000627:therapeutic use; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005290:Ferric Compounds / Q000627:therapeutic use; D005296:Ferrous Compounds / Q000627:therapeutic use; D005609:Free Radicals; D006900:Hydroxylation; D007105:Immune Complex Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007781:Lactoferrin / Q000627:therapeutic use; D008297:Male; D000644:Quaternary Ammonium Compounds / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D014657:Vasculitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
D001059:Apoproteins; D002712:Chlorides; D005290:Ferric Compounds; D005296:Ferrous Compounds; D005609:Free Radicals; D000644:Quaternary Ammonium Compounds; C039223:apolactoferrin; C038178:ammonium ferrous sulfate; D007781:Lactoferrin; D003676:Deferoxamine; C024555:ferric chloride; D004121:Dimethyl Sulfoxide