Bench-to-bedside review: Platelets and active immune functions - new clues for immunopathology?

Abstract

Platelets display a number of properties besides the crucial function of repairing damaged vascular endothelium and stopping bleeding; these are exploited to benefit patients receiving platelet component transfusions, which might categorize them as innate immune cells. For example, platelets specialize in pro-inflammatory activities, and can secrete a large number of molecules, many of which display biological response modifier functions. Platelets also express receptors for non-self-infectious and possibly non-infectious danger signals, and can engage infectious pathogens by mechanisms barely explained beyond observation. This relationship with infectious pathogens may involve other innate immune cells, especially neutrophils. The sophisticated interplay of platelets with bacteria may culminate in sepsis, a severe pathology characterized by significant reductions in platelet count and platelet dysfunction. How this occurs is still not fully understood. Recent findings from in-depth platelet signaling studies reveal the complexity of platelets and some of the ways they evolve along the immune continuum, from beneficial functions exemplified in endothelium repair to deleterious immunopathology as in systemic inflammatory response syndrome and acute vascular diseases. This review discusses the extended role of platelets as immune cells to emphasize their interactions with infectious pathogens sensed as potentially dangerous.

Figure 1

Hypothetical mechanisms by which platelet membrane CD40/CD40L and soluble CD40L might regulate interactions between immune cells. Platelets can interact with numerous immune cells such as B cells, T cells, neutrophils, macrophages, endothelial cells, natural killer (NK) cells and dendritic cells (DC). Interactions with these cells can induce numerous immune-related events as shown. Th, T-helper; Treg, regulatory T cell.