Kadiri C, Masliah J, Bachelet M, Vargaftig B B, Béréziat G
Department of Biochemistry, CNRS URA 1283, Faculté de Médecine Saint Antoine, Paris, France.
J Cell Biochem. 1989 Jun;40(2):157-64. doi: 10.1002/jcb.240400204.
The stimulation of cultured guinea pig alveolar macrophages by the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine, or by the phospholipid inflammatory mediator platelet activating factor (PAF) induced an increase in arachidonic acid release and its cyclooxygenase products. This release, which was mimicked by the association of threshold concentrations of the calcium ionophore A 23187 and of the protein kinase C activator tetradecanoyl phorbol acetate arose mainly from diacyl- and alkyl-acyl-phosphatidylcholine and phosphatidylinositol. Using [1-14C]arachidonic acid-labeled membranes as an endogenous substrate as well as dioleoyl-phosphatidyl [14C]ethanolamine as an exogenous substrate, we showed that phospholipase A2 activity of stimulated macrophages increases upon stimulation. Treatment of macrophages by prostaglandin E2 decreased the arachidonic acid release elicited by the chemotactic peptide and PAF. Furthermore, prostaglandin E2 increased and PAF decreased the cellular content in cyclic AMP. From these results we suggest that an initial stimulation of alveolar macrophages by a bacterial signal initiates the sequential activation of a phospholipase C and of phospholipase A2, leading to the release of PAF and eicosanoids. These mediators may in turn modulate the cell response by increasing or decreasing cyclic AMP, Ca2+, or diacyglycerol macrophage content.
趋化肽N-甲酰-L-甲硫氨酰-L-亮氨酰-L-苯丙氨酸或磷脂炎性介质血小板活化因子（PAF）对培养的豚鼠肺泡巨噬细胞的刺激，会导致花生四烯酸释放及其环氧化酶产物增加。钙离子载体A 23187的阈值浓度与蛋白激酶C激活剂十四酰佛波醇乙酸酯联合使用时可模拟这种释放，其主要源于二酰基和烷基酰基磷脂酰胆碱以及磷脂酰肌醇。使用[1-¹⁴C]花生四烯酸标记的膜作为内源性底物以及二油酰磷脂[¹⁴C]乙醇胺作为外源性底物，我们发现受刺激巨噬细胞的磷脂酶A2活性在刺激后增加。用前列腺素E2处理巨噬细胞可减少趋化肽和PAF引起的花生四烯酸释放。此外，前列腺素E2会增加而PAF会降低细胞内的环磷酸腺苷含量。从这些结果我们推测，细菌信号对肺泡巨噬细胞的初始刺激会引发磷脂酶C和磷脂酶A2的顺序激活，导致PAF和类花生酸的释放。这些介质可能反过来通过增加或减少环磷酸腺苷、Ca²⁺或二酰甘油在巨噬细胞中的含量来调节细胞反应。
