Functionally role of Toll-Like Receptor 4 expressed by blood platelets as inﬂammatory cells of the immunity
Blood platelets are anucleated cells which play a major role on primary hemostasis and well demonstrated other functions in inflammation. Platelets store and secrete a great variety of soluble factors, with immunomodulatory functions. They also contain transcription factors that exert non-genomic activities. Among numerous receptors expressed at the surface of platelets, they display Toll-Like Receptors (TLR) that are key molecules for the interaction between innate and adaptive immunity. Platelets can be activated in response to infectious stimulation, such as with a bacterial gram-negative Lipopolysaccharide (LPS) - the natural ligand of the TLR4, or peptides from the gp41, part of the HIV envelope. Moreover, stimulation with hemostatic or infectious agonists results in the differential secretion of panels of immunomodulatory products, that seems to be finely regulated. To further understand this regulatory process, we have studied the presence in the platelet cytosol of the majority of eukaryotic TLR4 pathways proteins. The engagement of the platelet TLR4 with two biochemically distinct LPS (smooth vs. rough) leads to a differential release of immunomodulatory products in platelet supernatants; those supernatants can then differently activate target cells such as peripheral blood mononuclear cells. These results demonstrate that the inflammatory response of human platelets is regulated by the nature of the stimulus, showing new evidence on the sentry role of these cells. Thus, my work is part of a novel study of the inflammatory function of blood platelets and the role of these cells as immune cells, essentially in the innate and inflammatory branch