Changes in arachidonic acid metabolism and the aggregation of polymorphonuclear leukocytes in rats with streptozotocin-induced diabetes.

Changes in lipid composition were examined in peritoneal polymorphonuclear leukocytes (PMNL) from rats with streptozotocin-induced diabetes. The largest changes associated with the lipids in PMNL prepared from rats with insulin-dependent diabetes mellitus were found in the composition of fatty acids of phospholipids although no consistent changes were noted in the amounts of phospholipids in individual classes. The relative amount of arachidonic acid was significantly reduced and that of linoleic acid was significantly increased in PMNL from diabetic rats. The extent of A23187-stimulated release of arachidonic acid from CGP and IGP in PMNL from diabetic rats was much smaller than that from normal PMNL. Moreover, there were decreases in the production of free arachidonic acid and its metabolites, such as LTB4 and 5-HETE by A23187-stimulated PMNL from diabetic rats as compared to PMNL from normal rats. Aggregation of PMNL provoked by A23187 was significantly suppressed in PMNL from diabetic rats. However, addition of free arachidonic acid or LTB4 to normal PMNL and to those from diabetic rats resulted in aggregation to similar extents, a result that supports a role for enhanced availability of endogenous arachidonic acid in the induction of the aggregation of PMNL from diabetic rats. The present results suggest that diabetes-associated changes in arachidonic acid metabolism might play a critical role in the modulation of aggregation of PMNL.