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

Background: IgE-mediated stimulation of human basophils and lung mast cells causes the synthesis of larger amounts of 1-acyl-2-acetyl-sn-gly cero-3-phosphocholine (1-acyl-2-acetyl-GPC) than 1-alkyl-2-acetyl-sn-g lycero-3-phosphocholine (platelet activating factor [PAF]). Methods: T o 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 amount s of histamine (greater-than-or-equal-to 10%) in most donors tested (2 0 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 tha n 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 speci fic PAF receptor antagonist, WEB 2086 (10 nmol/L to 10 mumol/L), inhib ited 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 Ca 2+ dependent activation of PAF. Similarly 1-acyl-2-acetyl-GPC (0.1 to 10 mumol/L) caused a concentration-dependent inhibition of PAF-activat ed histamine secretion (inhibitory concentration of 50% congruent-to 0 .2 mumol/L). Conclusions: Our data suggest that 1-acyl-2-acetyl-GPC ma y represent, under certain circumstances, a modulator of human basophi l mediator release via mechanisms shared with PAF.