Harsh D M, Blackwood R A
Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan, 48109-0244, USA.
Biochem Biophys Res Commun. 2001 Mar 30;282(2):480-6. doi: 10.1006/bbrc.2001.4601.
Phosphatidic acid (PA), the product of phospholipase D (PLD) metabolism, is not only an important second messenger in neutrophil signal transduction but PA generation increases membrane fusogenicity. Following neutrophil stimulation, PA formation can be detected in azurophil, specific, and plasma membrane vesicle subcellular fractions, suggesting a potential role for PA formation in granule-plasma membrane fusion. Neutrophil stimulation also activates phospholipase A(2) (PLA(2)) and the release of arachidonic acid. In vitro fusion of plasma membrane vesicles and specific granules with complex liposomes were dependent on PLA(2) (<10 microM Ca(2+)) while the presence of PA in the liposomes augmented the effects of PLA(2). Azurophil granules were extremely resistant to fusion (no fusion at 12 mM Ca(2+) even in the presence of PLA(2)). However, in the presence of both PA and PLA(2) fusion could be detected at <5 microM Ca(2+), suggesting a direct role for phospholipid metabolism in neutrophil degranulation.
磷脂酸（PA）是磷脂酶D（PLD）代谢的产物，它不仅是中性粒细胞信号转导中的重要第二信使，而且PA的生成会增加膜融合性。在中性粒细胞受到刺激后，可在嗜天青颗粒、特异性颗粒和质膜囊泡亚细胞组分中检测到PA的形成，这表明PA形成在颗粒 - 质膜融合中具有潜在作用。中性粒细胞刺激还会激活磷脂酶A2（PLA2）并释放花生四烯酸。质膜囊泡和特异性颗粒与复合脂质体的体外融合依赖于PLA2（钙离子浓度<10微摩尔），而脂质体中PA的存在会增强PLA2的作用。嗜天青颗粒对融合具有极强的抗性（即使在存在PLA2的情况下，在钙离子浓度为12毫摩尔时也不发生融合）。然而，在同时存在PA和PLA2的情况下，在钙离子浓度<5微摩尔时可检测到融合，这表明磷脂代谢在中性粒细胞脱颗粒中具有直接作用。
