A COMPARATIVE-STUDY OF THE EFFECTS OF 1-ACYL-2-ACETYL-SN-GLYCERO-3-PHOSPHOCHOLINE AND PLATELET-ACTIVATING-FACTOR ON HISTAMINE AND LEUKOTRIENE-C(4) RELEASE FROM HUMAN-LEUKOCYTES

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:92

Article

COLUMBO, M ; HOROWITZ, EM ; PATELLA, V ; KAGEYSOBOTKA, A ; CHILTON, FH ; LICHTENSTEIN, LM

关键词: HISTAMINE;    LTC(4);    BASOPHILS;    PHOSPHOLIPIDS;    PAF;   

DOI  :  10.1016/0091-6749(93)90176-G

来源: Elsevier

【 摘 要 】

Background: 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]). Methods: To study the biologic activity of 1-acyl-2-acetyl-GPC, we compared its effects and those of PAF on histamine and leukoinene C4 (LTC4) release from human mixed leukocytes that contained basophils. Results: 1-Acyl-2-acetyl-GPC (0.1 to 10 mumol/L) failed to release significant amounts of histamine (greater-than-or-equal-to 10%) in most donors tested (20 of 24), whereas PAF (0. 01 to 1 mumol/L) was active in 58%. I-Acyl-2-acetyl-GPC (0.1 to 10 mumol/L) was a stimulus for LTC4 release (132 +/- 30 ng/mug 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 congruent-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% congruent-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% congruent-to 0.2 mumol/L). Conclusions: 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.

【 授权许可】

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