Antimicrobial peptides from platelets.

The fact that platelets play a key role in host defense against infection has been demonstrated by the following observations(1): (a) platelets rapidly respond to sites of endovascular trauma and chemotactic stimuli associated with microbial colonization, and they are the earliest and predominant cells at sites of microbial colonization of vascular endothelium; (b) platelets have surface receptors and cytoplasmic granules comparable in structure and function to those of neutrophils, monocytes, or macrophages; (c) platelets adhere directly to, and may internalize, microbial pathogens, thereby enhancing their clearance from the bloodstream and limiting their potential for hematogenous dissemination; (d) bacterial, fungal, and protozoal pathogens are damaged or killed by activated platelets in vitro; (e) platelets are capable of initiating or amplifying complement fixation in the presence of microorganisms; (f) platelets generate oxygen metabolites which likely contribute to their antimicrobial activity; (g) platelets and leukocytes interact synergistically to exert enhanced antimicrobial functions in vitro; (h) thrombocytopenia increases susceptibility to and severity of certain infections. Importantly, rabbit and human platelets are now known to contain and release microbicidal proteins (termed platelet microbicidal proteins [PMPs] or thrombin-induced PMPs [tPMPs]) when stimulated with microorganisms or platelet agonists associated with infection in vitro. It is hypothesized that these microbicidal peptides accumulate locally at sites of endovascular damage or infection. Recent investigations have confirmed that tPMP-susceptible pathogens are less capable of proliferation or hematogenous dissemination in vivo as compared with their isogenic counterpart strains that are resistant to PMPs. Collectively, the above observations strongly suggest that platelets play key and multi-faceted roles in antimicrobial host defense which appear to be significantly mediated by PMPs and tPMPs. Copyright 1999 Harcourt Publishers Ltd.