CD40 LIGAND ON ACTIVATED PLATELETS TRIGGERS AN INFLAMMATORY REACTION OF ENDOTHELIAL-CELLS

CD40 ligand (CD40L, CD154), a transmembrane protein structurally relat ed to the cytokine TNF-alpha, was originally identified on stimulated CD4(+) T cells(1-3), and later on stimulated mast cells and basophils( 4). Interaction of CD40L on T cells with CD40 on B cells is of paramou nt importance for the development and function of the humoral immune s ystem(5). CD40 is not only constitutively present on B cells, but it i s also found on monocytes, macrophages and endothelial cells, suggesti ng that CD40L has a broader function in vivo. We now report that plate lets express CD40L within seconds of activation in vitro and in the pr ocess of thrombus formation in vivo. Like TNF-alpha and interleukin-1, CD40L on platelets induces endothelial cells to secrete chemokines an d to express adhesion molecules, thereby generating signals for the re cruitment and extravasation of leukocytes at the site of injury. Our r esults indicate that platelets are not only involved in haemostasis bu t that they also directly initiate an inflammatory response of the ves sel wall.