Platelet secretion in inflammatory and infectious diseases

Abstract

Platelets are small, anucleate circulating cells that possess a dynamic repertoire of functions spanning the hemostatic, inflammatory, and immune continuum. Once thought to be merely cell fragments with responses limited primarily to acute hemostasis and vascular wall repair, platelets are now increasingly recognized as key sentinels and effector cells regulating host responses to many inflammatory and infectious cues. Platelet granules, including α-granules and dense-granules, store hundreds of factors and secrete these mediators in response to activating signals. The cargo packaged and stored within platelet granules orchestrates communication between platelets and other circulating cells, augments host defense mechanisms to invading pathogens and tumor cells, and - in some settings - drives dysregulated and injurious responses. This focused review will highlight several of the established and emerging mechanisms and roles of platelet secretion in inflammatory and infectious diseases.

Keywords: Infection; inflammation; platelet; secretion.

Figure 1

Schematic representation of platelet secretion or exocytosis. Upon activating signals, granules fuse to the plasma membrane with the chaperone proteins Rab27a and Munc13-4. Vesicle and plasma membrane fusion is regulated through SNARE proteins (VAMP-8, SNAP-23 and STX-11).

Figure 2

Platelet secretion in atherosclerosis. Activated platelets roll along the endothelial monolayer via GPIbα/P-selectin. Thereafter, platelets adhere to vascular endothelium via β3 integrins, release proinflammatory compounds (IL-1β, CD40L, PF4 and RANTES), and induce expression of chemotaxins and adhesion molecules on endothelial cells, which help recruit circulating leukocytes. These leukocytes transmigration and form foam cells through the uptake of LDL. In this and other mechanisms, platelets provide the inflammatory basis for plaque formation and subsequent thrombosis upon plaque rupture.

Figure 3

Platelet secretion mediates tumorigenesis. Activated platelets bind to invading tumor cells, secreting growth factors, chemokines, proteases, and microparticles. In some instances, these secreted factors may augment host defense mechanisms to halt tumor invasion while in other settings, these factor may result in injurious tumor cell transendothelial migration.

Figure 4

Platelet secretion: an innate immune response to malaria. The CD36 receptor on platelets recognizes malaria-infected erythrocytes and secretes platelet factor 4 (PF4), which is basally present in α-granules of resting platelets. PF4 secreted from α-granules of activated platelets lyse the parasite digestive vesicles by killing the parasite within.