The Pathophysiological Relevance of Monocyte-platelet Interactions in Inflammatory Disease

Monocyte-platelet complexes are important in a number of chronic inflammatory diseases, including atherosclerosis, rheumatoid arthritis, and diabetes. Interactions between monocytes and platelets are predominantly mediated by divalent cation-dependent interactions between platelet P-selectin and P-selectin glycoprotein ligand-1 expressed on monocytes. After initial tethering, additional interactions involving CD40/CD40L and extracellular matrix metalloprotinase inducer are thought to induce firm adhesion through activation of β2 integrins. The engagement of P-selectin glycoprotein ligand-1 on monocytes induces a series of complex signaling pathways, which regulate cytoskeletal arrangement, β2 integrin activation, transcriptional activation of proinflammatory genes, and the activation of proinflammatory chemokines and cytokine expression. The induction of a proinflammatory phenotype in monocytes adherent to activated platelets promotes the inflammatory response and highlights the importance of monocyte-platelet complexes in inflammatory disease. Investigation into the molecular mechanisms governing monocyte-platelet interactions is integral to further understanding of these complexes and to the identification of novel therapeutic targets for the treatment of inflammatory diseases. The focus of this review, therefore, is to discuss mechanisms and functional consequences of monocyte-platelet complex formation.