INJURY TO ADULT HUMAN DERMAL MICROVASCULAR ENDOTHELIAL-CELLS IN-VITRO

Adult human dermal microvascular endothelial cells maintained in cultu re for four to eight passages after isolation were injured by activate d human neutrophils but were not injured by unstimulated cells. Injury was cytotoxic as indicated by release of Cr-51 from prelabeled cells. injury was partially inhibited with catalase, dimethylthiourea, and d eferoxamine, but was not blocked by superoxide dismutase. Injury was e nhanced following pretreatment with iron bound to the membrane-permeab le chelator 8-hydroxyquinoline, while neither iron alone nor the chela tor by itself enhanced injury. These data suggest that injury results from the generation of hydrogen peroxide by the activated neutrophils and its conversion to hydroxyl radical through an iron-dependent mecha nism. These cells appear to be similar to human umbilical vein endothe lial cells (HUVEC) in sensitivity to oxidant-induced injury. However, unlike HUVEC, these cells do not show the age-dependent decrease in se nsitivity to killing by activated neutrophils that is a characteristic feature of HUVEC. Nor do they show the same increase in spontaneous l ysis as a function of age that is characteristic of HUVEC.