Platelet activating factor-induced P-selectin expression in platelets and its related signal transduction.
OBJECTIVE
To study the intracellular signal transduction mechanisms of platelet activating factor (PAF)-induced platelet P-selectin expression.


METHODS
Human blood platelets were used to test the effect of PAF-induced P-selectin expression using flow cytometry.


RESULTS
PAF 20 nmol.L-1 elicited a moderate upregulation of P-selectin expression [(47.5 +/- 1.3)% vs control (3.8 +/- 0.9)%, P < 0.01]. Pretreatment with egtazic acid (EGTA) 2 mmol.L-1 and 5,5'- dimethyl-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetracetic acid (BAPTA) 200 mumol.L-1 to block Ca2+ influx or chelate the intracellular calcium, respectively, reduced P-selectin expression in response to PAF [(13.3 +/- 0.9)% and (16.8 +/- 1.9)% vs (47.5 +/- 1.3)% of PAF group, P < 0.01]. Inhibition of Na+/H+ exchange with amiloride (Ami) 400 mumol.L-1 resulted in an inhibition of P-selectin expression [(37.5 +/- 2.1)% vs (47.5 +/- 1.3)% of PAF group, P < 0.01]. Genistein (Gen) 300 mumol.L-1 to inhibit protein tyrosine phosphorylation showed similar effect [(29 +/- 4)% vs (47.5 +/- 1.3)% of PAF group, P < 0.01].


CONCLUSIONS
Multiple signal transduction pathways, including protein tyrosine phosphorylation, Na+/H+ exchange, and Ca2+ mobilization, mediated PAF-induced P-selectin expression.
Laboratory of Molecular Pharmacology, Hunan Medical University, Changsha 410078, China.
S
S
Zeng
F X
FX
Yi
Z G
ZG
Guo
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000097:blood*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015398:Signal Transduction; D015854:Up-Regulation
D019007:P-Selectin; D010972:Platelet Activating Factor