Platelet Factor 4

PF-4/CXCL4 is a member of the CXC chemokine family that is released from the alpha-granules of activated platelets. PF-4/CXCL4 binds with high affinity to heparin, with antiheparin, antiangiogenic and immunomodulatory activities. PF-4/CXCL4 plays a role in hematopoiesis and immune cell modulation. In megakaryocytes CXCL4 is synthesized, enclosed in vesicles, and transferred to the α granules from which it is secreted following platelet activation. CXCL4 expression is also found in microglia, monocytes and activated T-cells[1][2].
CXCL4 shows pleiotropic biological functions. Firstly, CXCL4 activates platelets, modulates platelet aggregation and stimulates release of α-granule proteins. CXCL4 has a role in heparin-induced thrombocytopenia (HIT). Secondly, CXCL4 inhibits endothelial cell proliferation and migration, leading to suppression of angiogenesis. Thirdly, CXCL4 expresses immunomodulatory activities, such as down-regulation of IFN- production by type 1 T-helper (Th1) cells and up-regulation of IL-4, IL-5, and IL-13 in type 2 T-helper (Th2) cells. Fourthly, CXCL4 influences hematopoiesis, inhibiting megakaryocytopoiesis and the proliferation of committed erythroid and granulocyte-macrophage colonies, as well as of primitive CD34+ progenitors. Moreover, CXCL4 is also highly upregulated in plasmacytoid dendritic cells (pDCs) in systemic sclerosis and dendritic cells (DCs) after severe trauma[1][2][3].