CD154 and its receptors. Binding of CD154 to its classical CD40 counter-receptor regulates numerous critical biological responses. These mainly include B-cell-dependent isotype switching, cell-mediated immunity (production of cytokines, chemokines, adhesion molecules, growth factors, matrix metalloproteinases and procoagulants) and apoptosis. We have also shown that this interaction regulates platelet activation and thrombosis. The interaction of CD154 with the αIIbβ3 platelet integrin is involved in thrombus stabilization and may provide a novel outside-in signaling pathway by which platelets can be activated. CD154 can also bind to the inactive conformation of α5β1, and this interaction was shown to induce activation of the human monocytic U937 cell line. Finally, αMβ2 can mediate CD154-dependent inflammatory responses; in particular, leukocyte adhesion and neointimal formation. The pathophysiological relevance of these novel CD154-mediated interactions in inflammation remains elusive and additional studies will be required to address this issue.