PMID- 2172014 OWN - NLM STAT- MEDLINE DCOM- 19901213 LR - 20190620 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 272 IP - 1-2 DP - 1990 Oct 15 TI - Fluoride activates diradylglycerol and superoxide generation in human neutrophils via PLD/PA phosphohydrolase-dependent and -independent pathways. PG - 19-24 AB - 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. FAU - Olson, S C AU - Olson SC AD - Department of Biochemistry, Emory University Medical School, Atlanta, GA 30322. FAU - Tyagi, S R AU - Tyagi SR FAU - Lambeth, J D AU - Lambeth JD LA - eng GR - AI122809/AI/NIAID NIH HHS/United States GR - CA46508/CA/NCI NIH HHS/United States GR - T32 DK07298/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (1,2-diacylglycerol) RN - 0 (Diglycerides) RN - 0 (Phosphatidic Acids) RN - 0 (Phosphatidylethanolamines) RN - 11062-77-4 (Superoxides) RN - 3K9958V90M (Ethanol) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - 82231-61-6 (diarachidonyl diglyceride) RN - 8ZYQ1474W7 (Sodium Fluoride) RN - EC 3.1.3.4 (Phosphatidate Phosphatase) RN - EC 3.1.4.4 (Phospholipase D) SB - IM MH - Diglycerides/*blood MH - Ethanol/pharmacology MH - Kinetics MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Neutrophils/drug effects/*metabolism MH - Phosphatidate Phosphatase/*blood MH - Phosphatidic Acids/blood MH - Phosphatidylethanolamines/blood MH - Phospholipase D/*blood MH - Sodium Fluoride/*pharmacology MH - Superoxides/*blood EDAT- 1990/10/15 00:00 MHDA- 1990/10/15 00:01 CRDT- 1990/10/15 00:00 PHST- 1990/10/15 00:00 [pubmed] PHST- 1990/10/15 00:01 [medline] PHST- 1990/10/15 00:00 [entrez] AID - 0014-5793(90)80439-P [pii] AID - 10.1016/0014-5793(90)80439-p [doi] PST - ppublish SO - FEBS Lett. 1990 Oct 15;272(1-2):19-24. doi: 10.1016/0014-5793(90)80439-p.