Platelets are the chief effector cells in hemostasis. However, recent evidence suggests that platelets have multiple roles in host defense against infection. Reports by us and others showed that platelets functionally contribute to protection against Staphylococcus aureus (S. aureus) infection. In the current study, the capacity of mouse platelets to participate in host defense against S. aureus infection was determined by assessing two possibilities. First, we determined the ability of platelets to kill S. aureus directly; and second, we tested the possibility that platelets enhance macrophage phagocytosis and intracellular killing of S. aureus. We report here evidence in support of both mechanisms. Platelets effectively killed two different strains of S. aureus. A clinical isolate of methicillin resistant S. aureus (MRSA) was killed by platelets (>40% killing in 2 h) in a thrombin-dependent manner while a methicillin sensitive strain (MSSA) was killed to equal extent but did not require thrombin. Interestingly, thrombin-stimulated platelets also significantly enhanced peritoneal macrophage phagocytosis of both MRSA and MSSA by >70%, and restricted intracellular growth by >40%. Enhancement of macrophage anti-S. aureus activities is independent of contact with platelets but is mediated through releasable products, namely IL-1β. These data confirm our hypothesis that platelets participate in host defense against S. aureus both through direct killing of S. aureus and enhancing the antimicrobial function of macrophages in protection against S. aureus infection.

Artículo de publicación ISIElevated numbers of activated platelets circulate in patients with chronic inflammatory diseases, including atherosclerosis and coronary disease. Activated platelets can activate the complement system. Although complement activation is essential for immune responses and removal of spent cells from circulation, it also contributes to inflammation and thrombosis, especially in patients with defective complement regulation. Proinflammatory activated leukocytes, which interact directly with platelets in response to vascular injury, are among the main sources of properdin, a positive regulator of the alternative pathway. The role of properdin in complement activation on stimulated platelets is unknown. Our data show that physiological forms of human properdin bind directly to human platelets after activation by strong agonists in the absence of C3, and bind nonproportionally to surface CD62P expression. Activation of the alternative pathway on activated platelets occurs when properdin is on the surface and recruits C3b or C3(H2O) to form C3b,Bb or a novel cell-bound C3 convertase [C3(H2O),Bb], which normally is present only in the fluid phase. Alternatively, properdin can be recruited by C3(H2O) on the platelet surface, promoting complement activation. Inhibition of factor H–mediated cell surface complement regulation significantly increases complement deposition on activated platelets with surface properdin. Finally, properdin released by activated neutrophils binds to activated platelets. Altogether, these data suggest novel molecular mechanisms for alternative pathway activation on stimulated platelets that may contribute to localization of inflammation at sites of vascular injury and thrombosis

Platelets are critical to hemostatic and immunological function, and are key players in cancer progression, metastasis, and cancer-related thrombosis. Platelets interact with immune cells to stimulate anti-tumor responses and can be activated by immune cells and tumor cells. Platelet activation can lead to complex interactions between platelets and tumor cells. Platelets facilitate cancer progression and metastasis by: (1) forming aggregates with tumor cells; (2) inducing tumor growth, epithelial-mesenchymal transition, and invasion; (3) shielding circulating tumor cells from immune surveillance and killing; (4) facilitating tethering and arrest of circulating tumor cells; and (5) promoting angiogenesis and tumor cell establishment at distant sites. Tumor cell-activated platelets also predispose cancer patients to thrombotic events. Tumor cells and tumor-derived microparticles lead to thrombosis by secreting procoagulant factors, resulting in platelet activation and clotting. Platelets play a critical role in cancer progression and thrombosis, and markers of platelet-tumor cell interaction are candidates as biomarkers for cancer progression and thrombosis risk.

This study investigated intercellular adhesion molecule-1 (ICAM-1), a membrane protein that mediates cell-to-cell adhesion and communication, as a mechanism through which the inflammatory response facilitates muscle regeneration after injury. Toxin-induced muscle injury to tibialis anterior muscles of wild-type mice caused ICAM-1 to be expressed by a population of satellite cells/myoblasts and myofibers. Myogenic cell expression of ICAM-1 contributed to the restoration of muscle structure after injury, as regenerating myofibers were more abundant and myofiber size was larger for wild-type compared with Icam1 À/À mice during 28 days of recovery. Contrastingly, restoration of muscle function after injury was similar between the genotypes. ICAM-1 facilitated the restoration of muscle structure after injury through mechanisms involving the regulation of myofiber branching, protein synthesis, and the organization of nuclei within myofibers after myogenic cell fusion. These findings provide support for a paradigm in which ICAM-1 expressed by myogenic cells after muscle injury augments their adhesive and fusogenic properties, which, in turn, facilitates regenerative and hypertrophic processes that restore structure to injured muscle.

Theoretical studies have predicted spatiotemporal organization of cell metabolism. Using a rapidly gated CCD camera, we demonstrate for the first time sustained traveling waves of NAD(P)H autofluorescence and protons in individual morphologically polarized living cells. Chemical concentration fronts moved in the direction of cell orientation, thus correlating dissipative structures with cell shape.