Elsevier

Blood Reviews

Volume 21, Issue 2, March 2007, Pages 99-111
Blood Reviews

Review
Platelet-neutrophil-interactions: Linking hemostasis and inflammation

https://doi.org/10.1016/j.blre.2006.06.001Get rights and content

Summary

Platelets are essential for primary hemostasis, but they also play an important pro-inflammatory role. Platelets normally circulate in a quiescent state. Upon activation, platelets can secrete and present various molecules, change their shape as well as the expression pattern of adhesion molecules. These changes are associated with the adhesion of platelets to leukocytes and the vessel wall. The interaction of platelets with neutrophils promotes the recruitment of neutrophils into inflammatory tissue and thus participates in host defense. This interaction of neutrophils with platelets is mainly mediated through P-selectin and ß2 and ß3 integrins (CD11b/CD18, CD41/CD61). Platelets can also interact with endothelial cells and monocytes. Adherent platelets promote the ‘secondary capture‘ of neutrophils and other leukocytes. In addition, platelets secrete neutrophil and endothelial activators inducing production of inflammatory cytokines. Thus, platelets are important amplifiers of acute inflammation.

Section snippets

Platelets

Platelets are unnucleated fragments of bone marrow megakaryocytes. They contain few viable mitochondria, glycogen, at least three types of morphologically different granules (α-granules, dense core granules, lysosomes), and a complex membranous system. α-granules contain adhesion molecules important for platelet-platelet interactions and platelet interactions with other blood cells, mitogenic factors, plasma proteins, and factors relevant for coagulation and fibrinolysis (Table 1). Dense

Integrins

Integrins are a large family of receptors which are constitutively expressed on the surface of almost all cells. They consist of transmembrane αß heterodimers and can bind extracellular matrix proteins as well as immunoglobulin-like adhesion molecules. Many cell-cell and cell-extracellular matrix interaction are regulated by integrins, which modulate important events in different biological processes, e.g. hemostasis, thrombosis, immunology, inflammation, cell adhesion, growth, differentiation

Chemokine receptors

Chemokine receptors are members of the G-protein-coupled receptor family.52, 53, 54, 55 Platelets express the chemokine receptors CCR1, CCR3, CCR4, CXCR1, and CXCR4 (Table 3) that bind proinflammatory and homeostatic chemokines. One important ligand for CCR4, which is present and functional on platelets,56, 57 is CCL17 (Thymus and Activation Regulated Chemokine, TARC). This chemokine alone is not a potent platelet agonist, but it can enhance platelet stimulation in the presence of other

Shape change

Upon activation by thrombin, ADP or TXA2, platelets undergo shape change, and secrete contents of α- and dense granules.79 Rearrangement of cytoskeletal proteins, including the disassembly of a microtubule ring, occurs as one of the very first steps and results in a shape change from a disc-shaped cell into an intermediate spherical shape cell. This is followed by actin polymerization and extension of filopodia.80, 81 Agonist-dependent phosphorylation of platelet myosin induces its

Acknowledgement

A.Z. is supported by a grant of the Deutsche Forschungsgemeinschaft (DFG AZ 428/2–1). The original work from K.L.’s lab is supported by grants from the National Institutes of Health HL58108, 55798 and 73361.

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