Columbo M, Horowitz E M, Patella V, Kagey-Sobotka A, Chilton F H, Lichtenstein L M
Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma & Allergy Center, Baltimore, MD 21224.
J Allergy Clin Immunol. 1993 Aug;92(2):325-33. doi: 10.1016/0091-6749(93)90176-g.
IgE-mediated stimulation of human basophils and lung mast cells causes the synthesis of larger amounts of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-2-acetyl-GPC) than 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor [PAF]).
To study the biologic activity of 1-acyl-2-acetyl-GPC, we compared its effects and those of PAF on histamine and leukotriene C4 (LTC4) release from human mixed leukocytes that contained basophils.
1-Acyl-2-acetyl-GPC (0.1 to 10 mumol/L) failed to release significant amounts of histamine (> or = 10%) in most donors tested (20 of 24), whereas PAF (0.01 to 1 mumol/L) was active in 58%. 1-Acyl-2-acetyl-GPC (0.1 to 10 mumol/L) was a stimulus for LTC4 release (132 +/- 30 ng/micrograms of histamine) with a potency of about 1000 times less than PAF. The kinetics of 1-acyl-2-acetyl-GPC-activated LTC4 release were similar to those of PAF (half-life approximately equal to 2 minutes). The specific PAF receptor antagonist, WEB 2086 (10 nmol/L to 10 mumol/L), inhibited both 1-acyl-2-acetyl-GPC- and PAF-mediated LTC4 release with the same potency (inhibitory concentration of 50% approximately equal to 1.5 mumol/L). Brief (2-minute) cell preincubation with 1-acyl-2-acetyl-GPC in the absence of extracellular Ca2+ induced a decrease in the subsequent Ca2+ dependent activation of PAF. Similarly, 1-acyl-2-acetyl-GPC (0.1 to 10 mumol/L) caused a concentration-dependent inhibition of PAF-activated histamine secretion (inhibitory concentration of 50% approximately equal to 0.2 mumol/L).
Our data suggest that 1-acyl-2-acetyl-GPC may represent, under certain circumstances, a modulator of human basophil mediator release via mechanisms shared with PAF.
与1-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱（血小板活化因子[PAF]）相比，IgE介导刺激人嗜碱性粒细胞和肺肥大细胞会导致合成更多的1-酰基-2-乙酰基-sn-甘油-3-磷酸胆碱（1-酰基-2-乙酰基-GPC）。
为研究1-酰基-2-乙酰基-GPC的生物学活性，我们比较了其与人嗜碱性粒细胞混合白细胞中PAF对组胺和白三烯C4（LTC4）释放的影响。
在大多数受试供体（24例中的20例）中，1-酰基-2-乙酰基-GPC（0.1至10 μmol/L）未能释放大量组胺（≥10%），而PAF（0.01至1 μmol/L）在58%的供体中具有活性。1-酰基-2-乙酰基-GPC（0.1至10 μmol/L）是LTC4释放的刺激物（132±30 ng/μg组胺），其效力约比PAF低1000倍。1-酰基-2-乙酰基-GPC激活的LTC4释放动力学与PAF相似（半衰期约等于2分钟）。特异性PAF受体拮抗剂WEB 2086（10 nmol/L至10 μmol/L）以相同效力抑制1-酰基-2-乙酰基-GPC和PAF介导的LTC4释放（50%抑制浓度约等于1.5 μmol/L）。在无细胞外Ca2+的情况下，用1-酰基-2-乙酰基-GPC对细胞进行短暂（2分钟）预孵育会导致随后PAF的Ca2+依赖性激活降低。同样，1-酰基-2-乙酰基-GPC（0.1至10 μmol/L）引起PAF激活的组胺分泌呈浓度依赖性抑制（50%抑制浓度约等于0.2 μmol/L）。
我们的数据表明，在某些情况下，1-酰基-2-乙酰基-GPC可能通过与PAF共有的机制代表人类嗜碱性粒细胞介质释放的调节剂。
