Fluoride activates diradylglycerol and Superoxide generation in human neutrophils via PLD/PA phosphohydrolase‐dependent and ‐independent pathways

Abstract
In contrast to the rapid, ethanol‐inhibited Superoxide generation by the receptor‐linked agonist formyl‐methionyl‐leucyl‐phenylalanine (fMLP), fluoride‐activated Superoxide generation occurs after a prolonged lag, and as shown herein is relatively ethanol‐insensitive. We have investigated fluoride‐activation of diradylglycerol generation and phospholipase D activity. Fluoride induces a very large increase in diradylglycerol mass (both 1,2‐diacylglycerol (DAG) and 1‐O‐alkyl,2‐acylglycerol (EAG)), with kinetics similar to Superoxide generation. Unlike fMLP‐activated diglyceride generation which is completely inhibited by ethanol, that produced by fluoride is only partially (30%) blocked. When the phosphatidylcholine pool is 3H‐prelabeled, fluoride activates both [3H]phosphatidic acid (PA) and [3H]diglyceride generation with similar kinetics. Partial inhibition of the production of these species by ethanol was seen, coincident with the appearance of [3H]phosphatidylethanol, indicating phospholipase D‐dependent transphosphatidylation had occurred. The data are consistent with the fluoride activation of PA and diglyceride generation by both phospholipase D‐dependent and ‐independent (presumably phospholipase C) mechanisms.

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