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 (O°-) 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.

Nitric oxide and arthritis

“…Once protonated, peroxynitrite can decompose to form the highly reactive hydroxyl radical *OH, as shown in Figure 1; however, the reactions indicated in Figure 1 have not yet been shown to occur in vivo. Production of such species may be linked to tissue destruction in inflammation (58). This story gains a curious twist from the recent observation that brain NOS synthesizes not only NO but also superoxide (59).…”

“…Increased blood flow should also potentiate the edema associated with inflammation. Indeed, NO appears to increase vascular leakiness in several (58,68,69), but not all (70), tissues. NO also inhibits the adhesion of blood neutrophils to endothelium through mechanisms which interfere with CD11/CD18 or which involve the scavenging of superoxide (71).…”

Formation of 8‐nitroguanine in DNA treated with peroxynitrite in vitro and its rapid removal from DNA by depurination

“…Increasing evidence now suggests that peroxynitrite is a major agent causing tissue damage induced by inflammation in vivo [9][10][11]. Peroxynitrite oxidizes sulfhydryl groups and induces membrane lipid peroxidation [12][13][14].…”

Polymorphonuclear leukocyte mediated oxidative inactivation of alpha-1-proteinase inhibitor: Modulation by nitric oxide

“…The pre-treatment of PMNL with LArg caused appreciable decrease in the superoxide and hydroxyl radical generation, the former being LArg concentration dependent. In addition to the mediating endothelial relaxation of vascular smooth muscle (46), inhibiting platelet aggregation and adhesion and mediating tissue damage (47,48) nitric oxide has also been found to modulate superoxide radical generation (11,16,17,18,49). In our studies inclusion of L-Arg.…”