Phosphatidylserine-specific phospholipase A1 stimulates histamine release from rat peritoneal mast cells through production of 2-acyl-1-lysophosphatidylserine
Phosphatidylserine-specific phospholipase A1 stimulates histamine release from rat peritoneal mast cells through production of 2-acyl-1-lysophosphatidylserine
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DOI：
10.1074/jbc.m104597200
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发表时间：
2001-08-10
影响因子：
4.8
通讯作者：
Inoue, K
中科院分区：
文献类型：
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作者：
Hosono, H;Aoki, J;Inoue, K
溶血磷脂酰丝氨酸 (1-酰基-24-lso-PS) 已被证明可刺激由 Fc epsilon RI（IgE 高亲和力受体）交联触发的大鼠腹膜肥大细胞 (RPMC) 释放组胺，但溶血磷脂酰丝氨酸产生的精确机制尚不清楚。在本研究中，我们表明磷脂酰丝氨酸具有特异性。磷脂酶 A(1)、PS-PLA(1) 在 Fc epsilon RI 交联剂存在下通过产生 2-acyl-1-lyso-PS 刺激 RPMC 释放组胺。 2-酰基-1-lyso-PS 的效力几乎与1-酰基-2-lyso-PS 相同。其中活性丝氨酸残基（Ser(166)）被丙氨酸残基取代的无催化活性的 PS-PLA 没有表现出这种活性。 sPLA(2)-IIA 是另一种能够在体外产生溶血-PS 的分泌性 PLA(2)，也是一种针对 RPMC 的较差的组胺诱导剂。 PS-PLA(1)显着刺激粗制RPMC释放组胺，表明lyso-PS主要来源于肥大细胞以外的细胞。与这种现象相一致的是，当 RPMC 与凋亡的 Jurkat 细胞混合时，该酶更有效地刺激组胺释放。在这些条件下，用PS-PLA(1)处理的凋亡细胞释放出具有不饱和脂肪酸的lyso-PS。最后，对 PS-PLA(1) 有亲和力的肝素完全阻断。酶的刺激作用。总之，PS-PLA(1)可以与硫酸乙酰肝素蛋白聚糖结合，有效水解凋亡细胞质膜上出现的PS，并刺激2-酰基-1-lyso-PS介导的肥大细胞活化。
Lysophosphatidylserine (1-acyl-24-lso-PS) has been shown to stimulate histamine release from rat peritoneal mast cells (RPMC) triggered by Fc epsilon RI (high affinity receptor for IgE) cross-linking, although the precise mechanism of lyso-PS production has been obscure. In the present study we show that phosphatidylserine-specific. phospholipase A(1), PS-PLA(1), stimulates histamine release from RPMC through production of 2-acyl-1-lyso-PS in the presence of Fc epsilon RI cross-linker. The potency of 2-acyl-1-lyso-PS was almost equal to that of 1-acyl-2-lyso-PS. A catalytically inactive PS-PLA, in which an active serine residue (Ser(166)) was replaced with an alanine residue did not show such activity. sPLA(2)-IIA, another secretory PLA(2) that is capable of producing lyso-PS in vitro, was also a poor histamine inducer against RPMC. PS-PLA(1) significantly stimulated histamine release from crude RPMC, indicating that lyso-PS is mainly derived from cells other than mast cells. In agreement with this phenomenon, the enzyme stimulated the histamine release more efficiently when RPMC were mixed with apoptotic Jurkat cells. Under these conditions, lyso-PS with unsaturated fatty acid was released from the apoptotic cells treated with PS-PLA(1). Finally, heparin, which has affinity for PS-PLA(1) completely blocked. the stimulatory effect of the enzyme. In conclusion, PS-PLA(1) may bind to heparan sulfate proteoglycan, efficiently hydrolyze PS appearing on plasma membranes of apoptotic cells, and stimulate mast cell activation mediated by 2-acyl-1-lyso-PS.