Inflammatory role of platelets in acute coronary syndromes

Abstract
Several lines of evidence support a role for platelets as inflammatory cells. Firstly, platelets provide a wide range of growth factors and inflammatory mediators by their release from intracellular storage organelles. Included in this group of mediators are several members of the chemokine family. In fact, platelet factor 4 and β-thromboglobulin, localised in platelet α-granules, represented the first chemokines to be discovered.3 In recent years, a number of CC- and CXC- as well as other cytokines—for example, CD40 ligand (CD40L)—have been found in these cells.3 4Second, platelets do not only contain and express inflammatory mediators, but may upon activation also induce the expression of such substances (for example, TNFα and chemokines) in monocytes/macrophages. Actually, upon activation platelets express P-selectin on their surface. Through ligation with its counterpart on monocytes/macrophages, P-selectin has the potential to enhance the activation of the transcriptional factor nuclear factor-κB,5 a factor required for expression of chemokines, TNFα and several other gene products playing a key role in inflammation. Notably, recent studies suggest that platelets also may modulate the function of other leucocyte subsets (for example, natural killer cells, granulocytes, and T cells) and they have been found to enhance chemotactic and adhesive properties of endothelial cells as well as IL-1 production in vascular smooth muscle cells (SMC).6 7 Finally, platelets may not only promote an inflammatory response in leucocytes and endothelial cells, but may also themselves respond to inflammatory mediators produced by these cells. In fact, platelets have recently been found to express several chemokine receptors that upon stimulation endorse platelet activation.8 In summary, upon activation platelets may release and express inflammatory mediators, induce an inflammatory response within leucocytes, and respond with activation to several of the inflammatory mediators produced by these cells. This platelet–leucocyte cross talk seems to involve a wide range of mediators such as chemokines, adhesions molecules, reactive oxygen species (ROS), and cytokines. It is tempting to hypothesise that this inflammatory interaction between platelets and leucocytes, also involving endothelial cells, may represent a vicious circle playing a pathogenic role not only in the chronic atherosclerotic process, but also in the triggering of the acute coronary syndromes.