Figure 3.
Platelets have activities that span the continuum from acute inflammation to adaptive immune responses. (A) Activated platelets can mediate inflammatory and immune responses using a variety of molecular mechanisms, including release of stored chemokines (β-thromboglobulin, platelet factor 4, ENA-78, Gro α, RANTES, SDF1α, and others), cytokines (HMBG1), and growth factors (PDGF, others). Activated platelets also synthesize lipid mediators including thromboxane A2 and PAF, which have inflammatory and immune activities. The spectrum of inflammatory factors released from activated platelets is reviewed in Refs. 34 and 45. (B) In addition to lipid mediators, platelets rapidly synthesize IL-1β. This occurs via a regulated post-transcriptional pathway. IL-1β can then remain cell associated or be released in solution or in association with microvessicles. When synthesized by activated platelets in vitro, IL-1β is deposited in fibrin clots; if this occurs in vivo, clots and thrombi may act as local reservoirs for the cytokine. Platelet-derived IL-1β can signal human endothelial cells, leading to synthesis of adhesion molecules and chemokines that mediate PMN accumulation and activation (54). Platelets can also induce inflammatory responses by display of CD40 ligand (CD40L), which is recognized by CD40 on the surfaces of endothelial cells (34). (C) Activated platelets display P-selectin, which can mediate their adhesion to monocytes by binding to PSGL-1 on the leukocyte surfaces. P-selectin acts in concert with other adhesion molecules on the platelet plasma membrane and with chemokines and cytokines released by the platelets to mediate intercellular signaling and inflammatory gene expression by the target leukocytes. Activated platelets can also bind to PMNs (see Figure 4) and lymphocytes and alter their responses (reviewed in Refs. 2 and 45). (D) Activated platelets can signal functional changes in dendritic cells using multiple molecular pathways, and can potentially also influence differentiation of monocyte precursors to dendritic cells or macrophages (reviewed in Ref. 45). This figure was modified from Ref. 45 with permission.