Korchak H M, Vienne K, Rutherford L E, Weissmann G
Fed Proc. 1984 Sep;43(12):2749-54.
In the neutrophil, binding of ligands to their appropriate receptors initiates a sequence of events culminating in the physiological responses of aggregation, degranulation, and superoxide anion generation. Calcium has been proposed as a second messenger in the activation sequence of the neutrophil. Increments in cytosolic free calcium are one of the first measurable events subsequent to receptor occupancy, followed by enhanced plasmalemmal permeability to calcium, a process that may serve to enhance the physiological responses. In contrast to calcium, cyclic AMP (cAMP) does not act as a signal in the activation sequence of the neutrophil. Increments in cAMP that are triggered by complete secretagogues may act as an inhibitory feedback mechanism. Protein kinases, both cAMP- and calcium/phospholipid-sensitive enzymes, may play a role in the activation sequence. Phosphorylation of proteins occurs during neutrophil activation. A role for phosphatidylinositol/phosphatidic acid turnover in calcium gating has been proposed. In addition, modulation of phospholipids could serve to activate a protein kinase C. Finally, phospholipids can serve as a source for arachidonic acid, which is metabolized by a 5-lipoxygenase pathway in the neutrophil. Products of this pathway, such as leukotriene B4, may serve to mediate or modulate the activation sequence.
在中性粒细胞中,配体与其相应受体的结合引发一系列事件,最终导致聚集、脱颗粒和超氧阴离子生成等生理反应。钙被认为是中性粒细胞激活序列中的第二信使。胞质游离钙的增加是受体占据后最早可测量的事件之一,随后是质膜对钙的通透性增强,这一过程可能有助于增强生理反应。与钙不同,环磷酸腺苷(cAMP)在中性粒细胞的激活序列中不作为信号。由完全促分泌剂触发的cAMP增加可能作为一种抑制性反馈机制。蛋白激酶,包括对cAMP和钙/磷脂敏感的酶,可能在激活序列中起作用。蛋白质磷酸化发生在中性粒细胞激活过程中。有人提出磷脂酰肌醇/磷脂酸周转在钙门控中起作用。此外,磷脂的调节可用于激活蛋白激酶C。最后,磷脂可作为花生四烯酸的来源,花生四烯酸在中性粒细胞中通过5-脂氧合酶途径代谢。该途径的产物,如白三烯B4,可能介导或调节激活序列。