on February 10, 2005
Published online before print February 10, 2005, doi: 10.1161/01.ATV.0000159094.17235.9b
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Submitted on February 3, 2004
Accepted on February 2, 2005
Effect of P-Selectin on Phosphatidylserine Exposure and Surface-Dependent Thrombin Generation on Monocytes
Ian Del Conde ;
From the Section of Cardiology (I.D.C., N.S.K.), Thrombosis Research Section (I.D.C., P.T., J.A.L., N.S.K.), Department of Pathology (P.T.), and Department of Medicine (F.N., R.T.), Baylor College of Medicine, Houston, Texas.
* To whom correspondence should be addressed. E-mail: nkleiman{at}bcm.tmc.edu.
Objective--Stimulation of monocytes with P-selectin induces the synthesis of an array of mediators of inflammation, as well as the expression of tissue factor (TF), the main initiator of coagulation. Because the membrane-bound reactions of coagulation are profoundly influenced by the presence of phosphatidylserine on the membranes of cells, factors that increase its expression may have an impact on coagulation.
Methods and Results--Using flow cytometry, we studied the effect of P-selectin on phosphatidylserine expression in blood monocytes and in the monocytic cells, THP-1. Soluble P-selectin at biologically relevant concentrations (0.31 to 2.5 µg/mL) induced a time-dependent increase in phosphatidylserine expression, an effect that could be inhibited with an anti-PSGL-1 blocking antibody, and by genistein, a tyrosine kinase inhibitor. Binding of activated platelets to THP-1 cells also resulted in a significant increase in phosphatidylserine expression that was dependent on PSGL-1. Consistent with the role of phosphatidylserine on surface-dependent reactions of coagulation, treatment of monocytic cells with soluble P-selectin led to increased thrombin generation. We excluded P-selectin induced apoptosis of monocyte as a mechanism for the increased phosphatidylserine exposure.
Conclusion--In summary, we show that P-selectin, either soluble or in its membrane-bound form, induces phosphatidylserine exposure in monocytes through a mechanism dependent on PSGL-1.
Key words: monocyte • platelet • phosphatidylserine • phospholipid • P-selectin
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