STIMULATION OF ENDOTHELIAL-CELLS BY PROTEASE ACTIVITY IN COMMERCIAL PREPARATIONS OF XANTHINE-OXIDASE

The O2 radical generating system of xanthine oxidase plus xanthine, which has been used as a model for the oxidative burst of activated granulocytes, is known to damage endothelium in vivo and in vitro. Effects (inhibited by catalase, and thus associated with the formation of H2O2) on several parameters of endothelial function were observed using a non-commercial preparation of xanthine oxidase. Xanthine oxidase from 2 different commercial sources has additional effects on endothelial morphology and ion flux that are substrate-independent (i.e., produced in the absence of added xanthine) and are attributable to the presence of pancreatin (a crude enzyme mixture used in the commercial preparation of xanthine oxidase from milk). These effects are related to the tryptic activity of pancreatin and extend previous observations on the effects of neutral proteases on endothelial cells. Studies on the effects of commercial xanthine oxidase preparations on endothelial cells must take account of their trypsin-like activity as well as their capacity to generate O2 products.