Stimulation of platelet-activating factor synthesis in polymorphonuclear leukocytes from streptozotocin-induced...

The platelet-activating factor (PAF)-synthesizing capacity was investigated and compared in peritoneal polymorphonuclear leukocytes (PMN) from streptozotocin-induced diabetic and normal rats. PAF synthesis was significantly enhanced in the PMN from diabetic rats compared with that from normal rats stimulated with fMLP. This was manifested as the increased incorporation of [3H]acetate into PAF. Selected ion monitoring/GC/MS analysis revealed that the molecular species of PAF synthesized were mostly of the 1-hexadecyl type, and the amount synthesized in fMLP-stimulated diabetic rat PMN was 1.5 times higher than that in normal rat PMN. The fMLP-induced arachidonic acid liberation resulting from phospholipase A2 activation, was facilitated with a concomitant increase in the cytosolic Ca2+ concentration in diabetic rat PMN. The CoA-independent transacylase activity was similar in both PMN lysates, whereas acetyl-CoA:lyso-PAF acetyltransferase activity was accelerated in the diabetic rat PMN lysate. These results revealed that diabetic rat PMN has more ability to synthesize PAF, presumably due to the large increase in activated phospholipase A2 and acetyltransferase, as well as the increased cytosolic Ca2+ concentration.