PMID- 3922982 OWN - NLM STAT- MEDLINE DCOM- 19850709 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 260 IP - 11 DP - 1985 Jun 10 TI - Lipoxygenase products of arachidonic acid modulate biosynthesis of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) by human neutrophils via phospholipase A2. PG - 6899-906 AB - When human neutrophils, previously labeled in their phospholipids with [14C]arachidonate, were stimulated with the Ca2+-ionophore, A23187, plus Ca2+ in the presence of [3H]acetate, these cells released [14C]arachidonate from membrane phospholipids, produced 5-hydroxy-6,8,11,14-[14C]eicosatetraenoic acid (5-HETE) and 14C-labeled 5S,12R-dihydroxy-6-cis,8,10-trans, 14-cis-eicosatetraenoic acid ([14C]leukotriene B4), and incorporated [3H]acetate into platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). Ionophore A23187-induced formation of these radiolabeled products was greatly augmented by submicromolar concentrations of exogenous 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE), 5-HETE, and leukotriene B4. In the absence of ionophore A23187, these arachidonic acid metabolites were virtually ineffective. Nordihydroguaiaretic acid (NDGA) and several other lipoxygenase/cyclooxygenase inhibitors (butylated hydroxyanisole, 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline and 1-phenyl-2-pyrazolidinone) caused parallel inhibition of [14C]arachidonate release and [3H]PAF formation in a dose-dependent manner. Specific cyclooxygenase inhibitors, such as indomethacin and naproxen, did not inhibit but rather slightly augmented the formation of these products. Furthermore, addition of 5-HPETE, 5-HETE, or leukotriene B4 (but not 8-HETE or 15-HETE) to neutrophils caused substantial relief of NDGA inhibition of [3H]PAF formation and [14C]arachidonate release. As opposed to [3H]acetate incorporation into PAF, [3H]lyso-PAF incorporation into PAF by activated neutrophils was little affected by NDGA. In addition, NDGA had no effect on lyso-PAF:acetyl-CoA acetyltransferase as measured in neutrophil homogenate preparations. It is concluded that in activated human neutrophils 5-lipoxygenase products can modulate PAF formation by enhancing the expression of phospholipase A2. FAU - Billah, M M AU - Billah MM FAU - Bryant, R W AU - Bryant RW FAU - Siegel, M I AU - Siegel MI LA - eng PT - Journal Article PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Acetates) RN - 0 (Arachidonic Acids) RN - 0 (Catechols) RN - 0 (Hydroxyeicosatetraenoic Acids) RN - 0 (Membrane Lipids) RN - 0 (Platelet Activating Factor) RN - 214IZI85K3 (Trifluoperazine) RN - 27YG812J1I (Arachidonic Acid) RN - 37H9VM9WZL (Calcimycin) RN - 467RNW8T91 (5-hydroxy-6,8,11,14-eicosatetraenoic acid) RN - 7BO8G1BYQU (Masoprocol) RN - EC 1.13.11.- (Arachidonate Lipoxygenases) RN - EC 1.13.11.12 (Lipoxygenase) RN - EC 3.1.- (Phospholipases) RN - EC 3.1.1.32 (Phospholipases A) RN - EC 3.1.1.4 (Phospholipases A2) RN - Q40Q9N063P (Acetic Acid) SB - IM MH - Acetates/metabolism MH - Acetic Acid MH - Arachidonate Lipoxygenases MH - Arachidonic Acid MH - Arachidonic Acids/*metabolism MH - Calcimycin/pharmacology MH - Catechols/pharmacology MH - Humans MH - Hydroxyeicosatetraenoic Acids/metabolism MH - Lipoxygenase/*metabolism MH - Masoprocol MH - Membrane Lipids/metabolism MH - Neutrophils/*metabolism MH - Phospholipases/*metabolism MH - Phospholipases A/*metabolism MH - Phospholipases A2 MH - Platelet Activating Factor/*biosynthesis MH - Trifluoperazine/pharmacology EDAT- 1985/06/10 00:00 MHDA- 1985/06/10 00:01 CRDT- 1985/06/10 00:00 PHST- 1985/06/10 00:00 [pubmed] PHST- 1985/06/10 00:01 [medline] PHST- 1985/06/10 00:00 [entrez] AID - S0021-9258(18)88865-2 [pii] PST - ppublish SO - J Biol Chem. 1985 Jun 10;260(11):6899-906.