Abstract
Incubation of murine spleen cells with the oxidation product of soybean lipoxidaseโtreated arachidonic acid results in profound inhibition of induction of proliferation and maturation of these cells. The active entity was shown to be the 15โhydroperoxide of arachidonic acid (15โHPAA). Inhibition of the enzymes of the cycloโoxygenase pathway fails to disturb this effect, indicating that 15โHPAA is not a substrate for this series of enzymes. 15โHPAA produced in this manner interfered with RNA synthesis, DNA synthesis, and blastogenesis, while failing to exert cytotoxic effects on the cells themselves. A variety of lymphocyte subpopulations, distinguished by their responsiveness to a diverse group of mitogens, were all equally inhibited by the addition of 15โHPAA to culture. Addition of this agent even as late as 24 h after initiation of culture resulted in profound inhibition of the proliferative and differentiative responses of splenic B cells to bacterial lipopolysaccharide (LPS). Exposure of cells to 15โHPAA for 10โ30 min was adequate to initiate inhibition, an event that exhibited marked temperature dependence. The effects of preโincubation with 15โHPAA could not be reversed in its absence in recovery periods of up to 6 h prior to addition of LPS. The implications of these data with reference to cellular activation mechanisms are discussed.