title: Biological effects of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine in the human neutrophil.
abstract: The synthesis of large quantities of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-2-acetyl-GPC) relative to 1-alkyl-2-acetyl-GPC (PAF; platelet-activating factor) has been demonstrated in several inflammatory cells. The present study has examined agonist and antagonist activities of 1-acyl-2-acetyl-GPC in the human neutrophil. 1-Acyl-2-acetyl-GPC induced a rapid increase in cytosolic calcium in the neutrophil; this effect was detected at 2 x 10(-9) M and was maximal at 10(-6) M. The peak response induced by 1-acyl-2-acetyl-GPC was similar to that induced by PAF although the potency of 1-acyl-2-acetyl-GPC was 300-fold lower than that of PAF. The dose response curves for both 1-acyl-2-acetyl-GPC and PAF were shifted in a parallel fashion by L-652,731 (10(-6) M), a PAF receptor antagonist, suggesting that both 1-acyl-2-acetyl-GPC and PAF act on the same receptor. High concentrations of 1-acyl-2-acetyl-GPC (10(-5) M) induced the release of beta-glucuronidase and lysozyme from the human neutrophil. The percent release of lysozyme induced by 1-acyl-2-acetyl-GPC was consistently higher than that of beta-glucuronidase. Prior stimulation of neutrophils with 1-acyl-2-acetyl-GPC dose-dependently inhibited the increase in cytosolic calcium induced by a subsequent challenge with an optimal concentration of PAF. Similarly, preincubation of neutrophils with 1-acyl-2-acetyl-GPC dose-dependently inhibited beta-glucuronidase and lysozyme release induced by a subsequent stimulation with PAF. The inhibitory effect on degranulation could not be surmounted even by concentrations of PAF 10-fold higher than that of 1-acyl-2-acetyl-GPC. The inhibition appeared to be selective for PAF since 1-acyl-2-acetyl-GPC did not affect f-met peptide-induced degranulation. This study suggests that 1-acyl-2-acetyl-GPC may act as a naturally-occurring specific inhibitor of PAF-induced activation of the human neutrophil.
authors.affiliation: Johns Hopkins University School of Medicine, Asthma and Allergy Center, Baltimore, MD.
authors.forename: M
authors.initials: M
authors.lastname: Triggiani
authors.forename: D W
authors.initials: DW
authors.lastname: Goldman
authors.forename: F H
authors.initials: FH
authors.lastname: Chilton
mesh_terms: D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D013268:Stimulation, Chemical
chemical_list: C069030:1-acyl-2-acetyl-sn-glycero-3-phosphocholine; D005663:Furans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran; D009113:Muramidase; D005966:Glucuronidase; D002118:Calcium