Recombinant Mouse CXCL4/PF4 Protein, CF

CXCL4, also called PF4 (platelet factor 4), is an 8 kDa member of the CXC chemokine family, sharing features with CXCL8/IL-8 and CXCL7/NAP-2 (1-3). Mature mouse CXCL4 shares 76%, 88%, 64%, 64% and 63% amino acid sequence identity with human, rat, ovine, porcine and bovine CXCL4, respectively. The active protein is a tetramer of CXCL4 subunits that forms a ring of heparin-binding positive charges from sites at the C-terminal region of each monomer (3). Megakaryocytes synthesize CXCL4 and store it in platelet alpha-granules (2, 3). Secretion from activated platelets can produce micromolar levels in serum and over 100‑fold higher within clots (2, 3). In contrast to other CXC chemokines, CXCL4 does not contain an ELR motif and lacks binding to nearly all chemokine receptors (2, 3). A potential high-affinity G-protein-coupled receptor for CXCL4, the CXCR3 isoform CXCR3B, is expressed in human but not mouse (2, 3). In most cases, it is likely that cell surface binding and signaling properties of CXCL4 are due to binding of glycosaminoglycans chains, particularly chondroitin sulfates (2). CXCL4 released from activated platelets binds and regulates thrombin/thrombomodulin complexes, regulates and enhances production of activated Protein C (APC), and limits the coagulation cascade (2-6). It binds and influences the enzymatic activity of coagulation factor Xa (7). It binds fibrin and affects clot structure (8). Therapeutic doses of the anticoagulant heparin neutralize CXCL4 procoagulant effects (9). The complex between heparin and CXCL4 can be immunogenic, and circulating CXCL4-heparin antibodies cause the human syndrome HITT (heparin-induced thrombocytopenia and thrombosis, also called HIT) (2). In addition, immunogenic complexes of CXCL4 with apolipoprotein H can contribute to antiphospholipid syndrome (APS) (10). CXCL4 can be antiproliferative and antiangiogenic, at least in part via interfering with FGF-2 and VEGF heparin binding and thus inhibiting their signaling (3, 11-13). However, it can also be proinflammatory and pro‑atherogenic through multiple effects on monocytes, macrophages and endothelial cells (2, 3).