The Platelet Response to Tissue Injury

Abstract

In recent years, various studies have increasingly explained platelet functions not only in their central role as a regulator in cellular hemostasis and coagulation. In fact, there is growing evidence that under specific conditions, platelets act as a mediator between the vascular system, hemostasis, and the immune system. Therefore, they are essential in many processes involved in tissue remodeling and tissue reorganization after injury or inflammatory responses. These processes include the promotion of inflammatory processes, the contribution to innate and adaptive immune responses during bacterial and viral infections, the modulation of angiogenesis, and the regulation of cell apoptosis in steady-state tissue homeostasis or after tissue breakdown. All in all platelets may contribute to the control of tissue homeostasis much more than generally assumed. This review summarizes the current knowledge of platelets as part of the tissue remodeling network and seeks to provide possible translational implications for clinical therapy.

Keywords: complement; cytokines; infection; inflammation; innate immunity; leukocytes; platelets; tissue remodeling.

Figure 1

Interactions of platelets and immune cells in the regulation of inflammation. Platelets express membrane receptors and produce soluble mediators such as chemokines which regulate the inflammatory response of immune cells. The interactions include monocytes, T-cells, neutrophils, and dendritic cells. DC, dendritic cells; EC, endothelial cells; ICAM-1, intercellular adhesion molecule 1; IL 6/8, interleukin 6/8; MCP1, monocyte chemotactic protein 1; TF, tissue factor; JAM C, junctional adhesion molecule C; PF4, platelet factor 4; PSGL-1, P-selectin glycoprotein ligand-1; RANTES, chemokine ligand 5 (CCL5); TNF α, tumor necrosis factor α; VCAM-1, vascular cell adhesion molecule 1.

Figure 2

Platelets in bacterial and viral infections. The role of platelets in infections may be underestimated. Platelets were shown to have a significant part in infectious diseases such as viral hepatitis, malaria, and listeriosis. Bct, bacteria; CD40L, cluster of differentiation 40 ligand; C3, complement component 3; cT-Cell, cytotoxic T-cell; DC, dendritic cell; GPIbα, glycoprotein Ibα; 5HT-R, 5-hydroxytryptamine-receptor; IL8, interleukin 8; LPS, lipopoly-saccharides; MAC, membrane attack complex; PF4, platelet factor 4; P-sel, P-selectin; RBC, red blood cell; ROS, reactive oxygen species; Ser, serotonin; Tcd 1/2, thrombocidin 1/2; TLR4, toll like receptor 4; TREM1, triggering receptor expressed on myeloid cells 1.

Figure 3

Platelets as regulators of angiogenesis. Platelets are able to both stimulate and inhibit the process of angiogenesis due to a variety of mediators stored in their granules. Furthermore, platelets are suggested to recruit circulating regenerative cells to the site of vascular lesion supported by soluble mediators. How these cells then contribute to tissue remodeling is still a matter of debate. BM-PC, bone marrow derived progenitor cells; bFGF, basic fibroblast growth factor, EC, endothelial cell; EGF, epidermal growth factor; HGF, hepatocyte growth factor; MMPs, matrix metalloproteinases; PDGF, platelet derived growth factor; PF4, platelet factor 4; P-sel, P-selectin; PSGL1, P-selectin glycoprotein ligand-1; PTL, platelet; S1P, sphingosine-1-phosphate; SDF-1, stromal cell-derived factor 1; TIMPs, tissue inhibitors of matrix metalloproteinases; TSP-1, thrombospondin 1; VEGF, vascular endothelial growth factor.