The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40

Recently, we have demonstrated that human platelets carry preformed CD40 li gand (CD154) molecules, which rapidly appear on the platelet surface follow ing stimulation by thrombin. Once on the surface, platelet CD154 induces an inflammatory reaction of CD40-bearing endothelial cells. This study shows that strong platelet agonists other than thrombin also lead to the expressi on of CD154 on the platelet surface. At the same time, several lines of evi dence are presented that together indicate that thrombotic events in the va sculature are generally accompanied by activation of the inflammatory poten tial of platelet CD154. This study also reports the constitutive expression of CD40, the receptor for CD154, on platelets. The binding of CD154 to coe xpressed CD40 in the platelet aggregate leads within minutes to hours to th e cleavage of membrane-bound surface CD154 and the release of an 18-kd solu ble form of the molecule. Soluble CD154 (sCD154), in contrast to transmembr ane CD154, can no longer induce an inflammatory reaction of endothelial cel ls. These findings indicate that the interaction of platelet CD154 with CD4 0 on neighboring cells is temporally limited to prevent an uncontrolled inf lammation at the site of thrombus formation. Thus, similar to the very tigh t regulation of the CD154-CD40 interaction in the immune system, an effecti ve mechanism controls the inflammatory potential of platelet CD154 in the v ascular system. (C) 2001 by The American Society of Hematology.