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

Michele Columbo, Edward M. Horowitz, Vincenzo Patella, Anne Kagey-Sobotka, Floyd H. Chilton, Lawrence M. Lichtenstein

Research output: Contribution to journalArticlepeer-review

Abstract

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 μmol/L) failed to release significant amounts of histamine (≥ 10%) in most donors tested (20 of 24), whereas PAF (0.01 to 1 μmol/L) was active in 58%. 1-Acyl-2-acetyl-GPC (0.1 to 10 μmol/L) was a stimulus for LTC4 release (132 ± 30 ng/μg 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 ≅ 2 minutes). The specific PAF receptor antagonist, WEB 2086 (10 nmol/L to 10 μmol/L), inhibited both 1-acyl-2-acetyl-GPC- and PAF-mediated LTC4 release with the same potency (inhibitory concentration of 50% ≅ 1.5 μmol/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 μmol/L) caused a concentration-dependent inhibition of PAF-activated histamine secretion (inhibitory concentration of 50% ≅ 0.2 μmol/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.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalThe Journal of allergy and clinical immunology
Volume92
Issue number2
DOIs
StatePublished - Aug 1993

Keywords

  • Histamine
  • LTC
  • PAF
  • basophils
  • phospholipids

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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