Summary
P-selectin is translocated from the α-granules to the surface of activated platelets
where it participates in thrombosis and inflammation. We investigated the signaling
pathways involved in thrombin-induced human platelet P-selectin expression. Assessed
by flow cytometry, inhibition of protein kinase C (PKC) with chelerythrine reduced
P-selectin expression by 66%, platelet/neutrophil binding, GPIIb/IIIa activation and
aggregation (p<0.05). Gö 6976, an inhibitor of the conventional PKCs (α and β), did
not alter P-selectin expression. However, rottlerin inhibited by 50% its expression
(p<0.05), but only at doses that interfere with the novel (є, η) and atypical (ζ)
PKCs. Inhibition of protein tyrosine kinase (PTK) and phosphoinositide 3-kinase (PI3-K)
did not significantly affect P-selectin expression. In conclusion, thrombin-induced
P-selectin expression is PKC-sensitive, but PTK and PI3-K-insensitive. The novel є
and η and atypical ζ, but not the conventional α and β and the novel θ PKCs, may be
involved in this process.
Keywords
Platelets - P-selectin - protein kinase C - protein tyrosine kinase - phosphoinositide
3-kinase