TY - JOUR
T1 - Biological effects of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine in the human neutrophil
AU - Triggiani, Massimo
AU - Goldman, Daniel W.
AU - Chilton, Floyd H.
N1 - Funding Information:
This work was supportedb y NIH grants A124985. A126771a nd A124283.D r. Triggiani is the recipiento f a ?'ogartyR esearchF ellowshipA ward(NIH, Bethesda).
PY - 1991/6/19
Y1 - 1991/6/19
N2 - 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 2·10-9 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 β-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 β-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 β-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.
AB - 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 2·10-9 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 β-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 β-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 β-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.
KW - 1-Acyl-2-acetyl-sn-glycero-3-phosphocholine
KW - Neutrophil
KW - Platelet-activating factor
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U2 - 10.1016/0005-2760(91)90053-K
DO - 10.1016/0005-2760(91)90053-K
M3 - Article
C2 - 1647203
AN - SCOPUS:0025802674
SN - 0005-2760
VL - 1084
SP - 41
EP - 47
JO - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
JF - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
IS - 1
ER -