title: Tissue injury caused by deposition of immune complexes is L-arginine dependent.
abstract: Nitric oxide (NO.), a free radical that is generated from L-arginine by stimulated endothelial cells, neutrophils, activated macrophages, and other cell types, reacts with superoxide anion (O2.-) to form peroxynitrite, which itself may be tissue toxic or can then react further to form the highly reactive and toxic hydroxyl radical (HO.). Because vascular injury produced by tissue deposition of immune complexes is linked to formation of toxic products derived from activated neutrophils, we have assessed whether immune complex-induced injury of rat lung and dermal vasculature is arginine dependent. The arginine analogue, NG-monomethyl-L-arginine (N-MeArg), which blocks NO. formation, protects against immune complex-induced vascular injury in rats. The protective effects of N-MeArg are reversed by the presence of L-arginine but not D-arginine. Additionally, in the absence of N-MeArg, injury is enhanced by the presence of L-arginine but not by D-arginine. Protection by N-MeArg is not associated with diminished recruitment of polymorphonuclear leukocytes. Bronchoalveolar lavage fluids from animals undergoing immune complex deposition in lung contain the decomposition products of NO.--namely, nitrite and nitrate. In the presence of N-MeArg these products are greatly diminished. These data suggest that immune complex-induced injury of rat lung and skin is L-arginine dependent. These data also suggest that in vivo metabolic products of L-arginine, such as NO(.), are directly or indirectly linked to immune complex-induced tissue injury.
authors.affiliation: Department of Pathology, School of Medicine, University of Michigan, Ann Arbor 48109.
authors.forename: M S
authors.initials: MS
authors.lastname: Mulligan
authors.forename: J M
authors.initials: JM
authors.lastname: Hevel
authors.forename: M A
authors.initials: MA
authors.lastname: Marletta
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D005609:Free Radicals; D007249:Inflammation; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000473:pathology*; D013481:Superoxides / Q000378:metabolism; D019323:omega-N-Methylarginine
chemical_list: D000936:Antigen-Antibody Complex; D005609:Free Radicals; D013481:Superoxides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D009195:Peroxidase