A comparative study of the effects of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine and platelet activating factor on histamine and leukotriene C4 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-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 leukotriene 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 (> 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).


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.
Columbo
M
M
Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma & Allergy Center, Baltimore, MD 21224.
Horowitz
E M
EM
Patella
V
V
Kagey-Sobotka
A
A
Chilton
F H
FH
Lichtenstein
L M
LM
D001491:Basophils / Q000187:drug effects / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013189:SRS-A / Q000378:metabolism*
C069030:1-acyl-2-acetyl-sn-glycero-3-phosphocholine; D010972:Platelet Activating Factor; D013189:SRS-A