Increase in microvascular permeability induced by enzymatically generated free radicals: I. In vivo study

Abstract

The inflammatory process is associated with the activation of phagocytic cells such as polymorphonuclear leukocytes with the subsequent release and generation into the extracellular space of a group of active compounds, some of which are free radicals. The relationship of these radical species to the other features of inflammation is unknown. The aim of this study was to assess the influence of free radicals generated by the aerobic oxidation of hypoxanthine by xanthine oxidase on the in vivo microvascular preparation of the hamster cheek pouch. Fluorescein-labeled Dextran, M w 150,000, was used to assess microvascular permeability. The application of xanthine oxidase alone or hypoxanthine and xanthine oxidase resulted in a significant increase in macromolecular extravasation which was not seen after addition of hypoxanthine, uric acid, or denatured enzyme. Increased leukocyte rolling and arteriolar vasoconstriction were also observed. The addition of xanthine oxidase to cheek pouch homogenates, in vitro, demonstrated that intrinsic cheek pouch substrates were available for enzyme-induced generation of superoxide anion radical. These results suggest that xanthine oxidase acting on exogenous and/or endogenous substrates generates a flux of free radicals which may further interact to result in the increased macromolecular permeability seen. It is suggested that the permeability changes seen during the inflammatory process may be in part related to the release of free radicals from inflammatory cells.