PF-4/CXCL4 Protein, Mouse (HEK293, Fc)

CXCL4, also known as PF-4 (platelet factor-4), is a member of the CXC chemokine family produced by cells of the megakaryocytic lineage.  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].
Mature human CXCL4 shares 70% amino acid sequence identity with mouse and rat CXCL4.
CXCL4 is stored in secretory granules of blood platelets and is released in response to protein kinase C and Rac1 activation. Platelets are considered to be the major cellular source of CXCL4. In the α-granules of blood platelets CXCL4 is kept as a tetramer bound to two molecules of chondroitin sulphate. CXCL4 does not possess an ELR acid sequence at its amino terminus and therefore does not bind to CXCR1 or CXCR2. CXCL4 moderates the effects of heparin-like molecules on the endothelial cell surface of blood vessels, thereby inhibiting local antithrombin III activity, which results in a procoagulant role of CXCL4. CXCL4 exhibits antiangiogenic properties in vitro and in vivo and inhibits tumor neovascularization through a variety of mechanisms. First, CXCL4 is able to interact directly with angiogenic growth factors, such as FGFs and VEGF, and inhibits their interaction with the cell surface receptor. Second, CXCL4 may bind proteoglycans and interfere with the proteoglycan-bystander effect on growth factor activity. Furthermore, a cell surface receptor that is expressed by human endothelial cells (ECs) in a cell cycle-dependent manner11 and mediates the antiangiogenic effects of CXCL4 has been recently identified and named as CXCR3-B. CXCL4 has been shown to modulate the proliferation, phenotype and function of immune cells. For instance, CXCL4 has been reported to promote monocyte survival and macrophage activation. CXCL4 induces migration of activated T lymphocytes^[1][2][3].
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].

Recombinant mouse CXCL4 protein (2.5, 5, 25, or 50 µg/kg/day) to myocardial infarction (MI) mice at 24 h post-MI by osmotic mini-pump. CXCL4 infusion dramatically reduces 7 day post-MI survival. CXCL4 infusion also increases Ccr4 and Itgb4 and decreased Adamts8 gene levels in the infarct region^[4].

Recombinant mouse CXCL4 (5 μg/mL; for 4 h) elicites macrophages to express pro-inflammatory cytokines in peritoneal macrophages. CXCL4 significantly up-regulates the expression of Ccl3, Ccl5, Il1β, and Il6^[4].
Recombinant mouse CXCL4 (20-2000 ng/mL; for 24 h) leads to dose-dependent increase in proliferation in stellate cells. CXCL4 also induces the directed migration of stellate cells in a modified Boyden chamber. Incubation of stellate cells with Cxcl4 for 24 hours leads to increased expression of Ccl5 mRNA and Ccl5 protein^[5].