Evidence for participation of hydroxyl radical in increased microvascular permeability.
Polymorphonuclear leukocytes undergo the respiratory burst when exposed to a variety of stimuli. This is associated with the production of superoxide anion radical (O-2). Dismutation of O-2 can occur spontaneously to produce hydrogen peroxide (H2O2) and in the presence of metal catalysts O-2 and H2O2 can react to form hydroxyl radical (OH.). Some of these reactive species are released into the interstitium and may cause lipid peroxidation and depolymerization of macromolecules. We have studied the effect of free radicals on vascular permeability. Hypoxanthine and xanthine oxidase were applied topically on the hamster cheek pouch microcirculation model, injected intravenously with FITC-dextran 150 (Mw 150,000) to visualize permeability changes. This caused a flux of O-2 and a significant increase in macromolecular leakage. An attempt was made to elucidate the roles of different radicals by addition of superoxide dismutase (SOD), catalase (CAT), dimethyl sulfoxide (DMSO) and L-methionine to the reaction mixture. A significant decrease in leakage was found with all these substances, indicating OH. or possibly singlet oxygen damage. These results indicate that a free radical flux can cause permeability changes, and we suggest that part of the permeability change seen during inflammation may be related to free radical flux produced by activated leukocytes.
D000818:Animals; D002199:Capillary Permeability; D002374:Catalase / Q000494:pharmacology; D006224:Cricetinae; D003911:Dextrans / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005609:Free Radicals; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D007249:Inflammation / Q000097:blood; D008715:Methionine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D003911:Dextrans; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D008715:Methionine; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D004121:Dimethyl Sulfoxide