Activation of human neutrophils with 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycerol-3-phosphorylcholine (platelet activating factor).
Activation of human neutrophils with 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycerol-3-phosphorylcholine (platelet activating factor).
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DOI：
10.4049/jimmunol.127.3.1250
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发表时间：
1981-09
影响因子：
4.4
通讯作者：
J. O. Shaw;R. N. Pinckard;K. S. Ferrigni;L. McManus;D. Hanahan
中科院分区：
文献类型：
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作者：
J. O. Shaw;R. N. Pinckard;K. S. Ferrigni;L. McManus;D. Hanahan
1-O-十六烷基/十八烷基-2-乙酰基-sn-甘油基-3-磷酸胆碱（AGEPC）是一种已知为血小板活化因子的乙酰化烷基磷酸甘油酯，在10（-10）至10（-5）M浓度范围内可刺激人中性粒细胞（PMN）胞吐、迁移、超氧化物产生和聚集。AGEPC诱导的PMN胞吐的嗜天青（髓过氧化物酶和β-葡萄糖醛酸酶）和特定的（乳铁蛋白和溶菌酶）溶酶体颗粒是快速的（T1/2 = 20秒），依赖于细胞松弛素B的存在下，但不与细胞质LDH的释放。正如所看到的补体衍生肽刺激，C5 a，AGEPC启动的PMN酶释放依赖于温度和细胞糖酵解，但不存在细胞外Ca++。当通过梯度分析分析时，由AGEPC引起的PMN迁移本质上主要是趋化性的。酶分泌和迁移的一个不寻常的特征是在10（-6）M和10（-5）M AGEPC之间反应降低。这种降低的反应性可以解释为在高AGEPC浓度下发生的快速PMN脱敏，限制了整体细胞反应。在细胞松弛素B不存在的情况下，用AGEPC刺激PMN，证实了对胞吐作用的快速脱敏。当随后加入细胞松弛素B并用AGEPC或C5 a攻击PMN时，发生对AGEPC而不是C5 a诱导的溶酶体酶释放的刺激特异性脱敏。对C5 a脱敏的PMN对随后的AGEPC激发反应正常。从AGEPC（lyso GEPC）中去除2-乙酰基后，检查的所有PMN功能的刺激均显著减弱。这些结果表明，AGEPC刺激各种各样的人PMN反应的受体样机制，依赖于短链脂肪酸酯在2-位的烷基磷酸甘油酯。
1-O-Hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), the acetylated alkyl phosphoglyceride known as platelet-activating factor, stimulated human neutrophil (PMN) exocytosis, migration, superoxide production and aggregation over a concentration range of 10(-10) to 10(-5) M. AGEPC-induced PMN exocytosis of azurophilic (myeloperoxidase and beta-glucuronidase) and specific (lactoferrin and lysozyme) lysosomal granules was rapid (T 1/2 = 20 sec), dependent on the presence of cytochalasin B, but was not associated with release of cytoplasmic LDH. As seen with the complement-derived peptide stimulus, C5a, AGEPC-initiated PMN enzyme release was dependent on temperature and cellular glycolysis but not on the presence of extracellular Ca++. When analyzed by gradient analysis, PMN migration caused by AGEPC was primarily chemotactic in nature. An unusual feature for both enzyme secretion and migration was a decrease in response between 10(-6) M and 10(-5) M AGEPC. This decreased responsiveness could be explained by rapid PMN desensitization occurring at high AGEPC concentrations, limiting the overall cellular response. Rapid desensitization for exocytosis was demonstrated in PMN stimulated with AGEPC in the absence of cytochalasin B. When cytochalasin B was added subsequently and PMN challenged with AGEPC or C5a, stimulus-specific desensitization to AGEPC but not C5a-induced lysosomal enzyme release occurred. PMN desensitized to C5a responded normally to a subsequent AGEPC challenge. Stimulation of all the PMN functions examined was markedly attenuated with removal of the 2-acetyl group from AGEPC (lyso GEPC). These results suggest that AGEPC stimulates a wide variety of human PMN responses by a receptor-like mechanism, dependent on the short chain fatty acid ester in the 2-position of the alkyl phosphoglyceride.