Korchak H M, Serhan C N, Weissmann G
Monogr Pathol. 1982(23):83-93.
The stimulus-response coupling sequence of neutrophils has been partially elucidated, and a temporal order for some of the initial events in PMN activation has been established; membrane potential, Ca2+ motivation, Ca2+ influx, cAMP pulse, aggregation, O2- . generation and degranulation. Receptor-ligand interaction is followed by membrane hyperpolarization and the mobilization of Ca2+ from intracellular loci. In common with other secretory cells, neutrophils utilize Ca2+ as a second messenger to mediate cellular responses. For optimal activation, neutrophils require an influx of extracellular Ca2+. However, the mechanism by which Ca2+ enters neutrophils or other cells is not known. In view of our recent findings that phosphatidic acid and oxidized trienoic acids can translocate Ca2+ in lipid bilayers, it should be apparent that a study of phospholipid metabolism (particularly changes in phosphatidyl inositol and phosphatidic acid) in human neutrophil activation together with a temporal analysis of Ca2+ influx will contribute to an understanding of the mechanism of stimulus-secretion coupling. Since arachidonic acid metabolites play an important role in inflammation and have recently been suspected of modulating stimulus-secretion coupling, studies of the release of arachidonic acid from membrane phospholipids are important because all prostaglandins and hydroxy acids are derived from this initial step. Finally, the generation, by neutrophils, of free arachidonic acid and its oxygenation products might serve as a model system for other tissues in addition to their important role in inflammation.
中性粒细胞的刺激-反应偶联序列已部分阐明，并且已确定了PMN激活中一些初始事件的时间顺序；膜电位、Ca2+动员、Ca2+内流、cAMP脉冲、聚集、O2-生成和脱颗粒。受体-配体相互作用之后是膜超极化和Ca2+从细胞内位点的动员。与其他分泌细胞一样，中性粒细胞利用Ca2+作为第二信使来介导细胞反应。为了实现最佳激活，中性粒细胞需要细胞外Ca2+的内流。然而，Ca2+进入中性粒细胞或其他细胞的机制尚不清楚。鉴于我们最近发现磷脂酸和氧化三烯酸可以在脂质双层中转运Ca2+，显然对人类中性粒细胞激活中磷脂代谢（特别是磷脂酰肌醇和磷脂酸的变化）的研究以及对Ca2+内流的时间分析将有助于理解刺激-分泌偶联的机制。由于花生四烯酸代谢产物在炎症中起重要作用，并且最近被怀疑调节刺激-分泌偶联，因此研究花生四烯酸从膜磷脂中的释放很重要，因为所有前列腺素和羟基酸都源自这一初始步骤。最后，中性粒细胞产生的游离花生四烯酸及其氧化产物除了在炎症中起重要作用外，还可能作为其他组织的模型系统。
