CALCIUM REGULATION OF THE HUMAN-PMN CYTOSOLIC 15-LIPOXYGENASE

Addition of tracer (pg) amounts of [H-3]arachidonic acid to the 120 000 x g cytosolic fraction of human polymorphonuclear leukocytes (PMNs) produced [H-3]-15-HETE, the product of the 15-lipoxygenase, as the major metabolite. In the presence of nanomolar and low micromolar amounts of calcium, [H-3]-15-HETE formation was increased as much as 15-fold which corresponded to 17% conversion of added substrate. This enhancement of the cytosolic 15-lipoxygenase activity, which was reversible by EGTA, was inhibited by phosphatidyl serine and phosphatidyl choline. Millimolar levels of calcium inhibited the cytosolic 15-lipoxygenase and the 5-lipoxygenase product 5-HETE could reverse this inhibition. These results indicate that calcium is an important modulator of the PMN 15-lipoxygenase when the enzyme is in a cytosolic milieu.