Superoxide anion participation in human monocyte-mediated oxidation of low-density lipoprotein and conversion of low-density lipoprotein to a cytotoxin.

摘要: Human monocytes, upon activation with opsonized zymosan, altered low-density lipoprotein (LDL) during a 24-h co-incubation, resulting in its oxidation and acquisition of cytotoxic activity against target fibroblast cell lines. Both the LDL conversion to cytotoxin were enhanced time incubation, most substantial changes occurring after 6 h culture activated monocytes. Unactivated monocytes did not mediate either alteration. Superoxide anion (O2-) participated both since addition superoxide dismutase (SOD) at beginning co-incubation inhibited, concentration dependent fashion, monocyte-mediated cytotoxin. As expected, rate release was greatest respiratory burst, very early incubation (0 2 h); however, exposure burst required for oxidation. The lower levels O2- released by cells hours had subsided sufficient lead initiation Three results indicated that oxidative modification into O2(-)-independent free radical propagation O2(-)-dependent initiation. First, exposed activated, anion-releasing could be almost completely blocked general scavenger butylated hydroxytoluene, but SOD. Second, proceeded even removal from anion-producing, various durations exposure. Third, development lipid peroxidation products greater cytotoxicity occurred cells, long peak subsided. These us conclude LDL, leading transformation cytotoxin, requires as result necessarily also propagation. potent toxin may explain tissue damage atherosclerotic lesions other pathologic sites which inflammatory congregate.