Diacylglycerols Modulate Human Polymorphonuclear Neutrophil Responsiveness: Effects on Intracellular Calcium Mobilization, Granule Exocytosis, and Superoxide Anion Production

The synthetic diacylglycerols (DG), sn‐1,2‐dihexanoylglycerol (diC 6 ), sn‐1,2‐dioctanoyl‐glycerol (diC 8 ), and 1‐oleoyl‐2‐acetylglycerol (OAG) stimulated the release of granule constituents from and superoxide anion (Of) generation by human polymorphonuclear neutrophils (PMN). The DGs did not induce a rise in the cytosolic‐free calcium concentration ([Ca 2+ ] i ), as monitored by the fluorescence of PMNs loaded with the fluorescent CA 2+ indicator, Fura‐2. DiC 6 , diC 8 , and OAG inhibited PMN degranulation elicited with the receptor‐specific ligands, N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP), acetylsn‐glyceryl‐3‐phosphorylcholine (AGEPC), and 5(S),12(R)‐dihydroxy‐6,14‐cis‐8,10‐trans‐eicosatetraenoic acid (LTB 4 ) and the calcium ionophore, A23187. In contrast to their inhibitory effects on granule exocytosis, diC 6 , diC 8 and OAG enhanced FMLP‐, AGEPC‐, LTB 4 and A23187‐stimulated O 2 ‐ production. Activation of the respiratory burst with phorbol 12‐myristate 13‐acetate (PMA) was unaffected by the DGs. DiC 8 inhibited the rise in [Ca 2+ ] i elicited with FMLP, LTB 4 , and AGEPC; this effect, as well as the DG‐mediated suppression of degranulation, could be reversed with the protein kinase C (PKC) inhibitor, 1‐(‐5‐isoquinolinesulfonyl)‐2‐methylpiperazine hydrochloride (H‐7). These data indicate that in addition to possessing the intrinsic capacity to activate PMNs, DG may function in a PKC‐mediated autoregulatory mode to influence PMN activation in a response‐specific manner by affecting certain components of receptor‐coupled and receptor‐independent signal transduction systems in a stimulus‐specific manner.