Inhibition of protein tyrosine phosphatases suppresses P-selectin exocytosis in activated human platelets.
P-selectin (CD62P), a cell adhesion molecule for most leukocytes, is stored in the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells. Upon thrombogenic and inflammatory challenges, P-selectin is rapidly expressed, by exocytosis, on activated platelets and stimulated endothelial cells. However, little is known with regard to the molecular mechanisms governing the regulation of the rapid mobilization of P-selectin in these cells. Here we show that phenylarsine oxide (PAO) and diamide (both were inhibitors for protein tyrosine phosphatases), but not genistein (an inhibitor for protein tyrosine kinases), adenosine, wortmannin, and LY294002 (all inhibitors for phosphatidylinositol 3- and 4-kinases), could inhibit P-selectin exocytosis on activated platelets and could abolish the P-selectin-mediated aggregation of activated platelets to neutrophils. However, PAO did not attenuate the P-selectin-mediated adhesion of human promyeloid HL-60 cells on the stimulated endothelial cells under flow conditions. Further, PAO had no detectable effects on the exocytosis of P-selectin in the stimulated endothelial cells. These results indicate that protein tyrosine phosphatases are necessary for P-selectin exocytosis on the activated platelets, but not on the stimulated endothelial cells, and suggest that inhibitors for protein tyrosine phosphatases may be potentially valuable for treatment of platelet/leukocyte aggregation.
Chen
M
M
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai, 200031, China.
Geng
J G
JG
D001152:Arsenicals / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002448:Cell Adhesion; D002478:Cells, Cultured; D003958:Diamide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis; D018922:HL-60 Cells; D006801:Humans; D007150:Immunohistochemistry; D009504:Neutrophils / Q000276:immunology; D019007:P-Selectin / Q000378:metabolism* / Q000502:physiology; D015539:Platelet Activation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D012397:Rosette Formation
D001152:Arsenicals; D004791:Enzyme Inhibitors; D019007:P-Selectin; C029341:oxophenylarsine; D003958:Diamide; D017027:Protein Tyrosine Phosphatases