Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif) ligand 4 (CXCL4) . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation.[1] It is usually found in a complex with proteoglycan.
Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair.[1][3]
The heparin:PF4 complex is the antigen in heparin-induced thrombocytopenia, an idiosyncratic autoimmune reaction to the administration of the anticoagulant heparin.[5] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.[6]
↑ 1.01.1Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M (July 1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood. 76 (2): 336–44. PMID1695112.
↑O'Donovan N, Galvin M, Morgan J (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenet Cell Genet. 84 (1–2): 39–42. doi:10.1159/000015209. PMID10343098.
↑Love MS, Millholland MG, Mishra S, Kulkarni S, Freeman KB, Pan W, Kavash RW, Costanzo MJ, Jo H, Daly TM, Williams DR, Kowalska MA, Bergman LW, Poncz M, Degrado WF, Sinnis P, Scott RW, Greenbaum DC (December 2012). "Platelet Factor 4 Activity against P. falciparum and Its Translation to Nonpeptidic Mimics as Antimalarials". Cell Host Microbe. 12 (6): 815–23. doi:10.1016/j.chom.2012.10.017. PMID23245326.
Further reading
Bikfalvi A, Gimenez-Gallego G (2004). "The control of angiogenesis and tumor invasion by platelet factor-4 and platelet factor-4-derived molecules". Semin. Thromb. Hemost. 30 (1): 137–144. doi:10.1055/s-2004-822978. PMID15034805.
Maurer AM, Zhou B, Han ZC (2007). "Roles of platelet factor 4 in hematopoiesis and angiogenesis". Growth Factors. 24 (4): 242–252. doi:10.1080/08977190600988225. PMID17381065.
Walz DA, Wu VY, de Lamo R, et al. (1978). "Primary structure of human platelet factor 4". Thromb. Res. 11 (6): 893–898. doi:10.1016/0049-3848(77)90117-7. PMID601757.
Nath N, Lowery CT, Niewiarowski S (1975). "Antigenic and antiheparin properties of human platelet factor 4 (PF4)". Blood. 45 (4): 537–50. PMID803847.
Hermodson M, Schmer G, Kurachi K (1977). "Isolation, crystallization, and primary amino acid sequence of human platelet factor 4". J. Biol. Chem. 252 (18): 6276–9. PMID893407.
Maione TE, Gray GS, Petro J, et al. (1990). "Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides". Science. 247 (4938): 77–79. doi:10.1126/science.1688470. PMID1688470.
Han ZC, Bellucci S, Tenza D, Caen JP (1990). "Negative regulation of human megakaryocytopoiesis by human platelet factor 4 and beta thromboglobulin: comparative analysis in bone marrow cultures from normal individuals and patients with essential thrombocythaemia and immune thrombocytopenic purpura". Br. J. Haematol. 74 (4): 395–401. doi:10.1111/j.1365-2141.1990.tb06325.x. PMID2140694.
Poncz M, Surrey S, LaRocco P, et al. (1987). "Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line". Blood. 69 (1): 219–23. PMID3098319.
Griffin CA, Emanuel BS, LaRocco P, et al. (1987). "Human platelet factor 4 gene is mapped to 4q12----q21". Cytogenet. Cell Genet. 45 (2): 67–69. doi:10.1159/000132431. PMID3622011.
Brown KJ, Parish CR (1994). "Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor". Biochemistry. 33 (46): 13918–13927. doi:10.1021/bi00250a047. PMID7524669.
Mayo KH, Roongta V, Ilyina E, et al. (1995). "NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N-terminal chimera: a symmetric tetramer". Biochemistry. 34 (36): 11399–11409. doi:10.1021/bi00036a012. PMID7547867.
Barker S, Mayo KH (1995). "Quarternary [sic] structure amplification of protein folding differences observed in 'native' platelet factor-4". FEBS Lett. 357 (3): 301–304. doi:10.1016/0014-5793(94)01384-D. PMID7835432.
Zhang X, Chen L, Bancroft DP, et al. (1994). "Crystal structure of recombinant human platelet factor 4". Biochemistry. 33 (27): 8361–8366. doi:10.1021/bi00193a025. PMID8031770.
Horne MK (1993). "The effect of secreted heparin-binding proteins on heparin binding to platelets". Thromb. Res. 70 (1): 91–98. doi:10.1016/0049-3848(93)90226-E. PMID8511754.
Kolset SO, Mann DM, Uhlin-Hansen L, et al. (1996). "Serglycin-binding proteins in activated macrophages and platelets". J. Leukoc. Biol. 59 (4): 545–54. PMID8613703.
1pfm: PF4-M2 CHIMERIC MUTANT WITH THE FIRST 10 N-TERMINAL RESIDUES OF R-PF4 REPLACED BY THE N-TERMINAL RESIDUES OF THE IL8 SEQUENCE. MODELS 1-15 OF A 27-MODEL SET.
1pfn: PF4-M2 CHIMERIC MUTANT WITH THE FIRST 10 N-TERMINAL RESIDUES OF R-PF4 REPLACED BY THE N-TERMINAL RESIDUES OF THE IL8 SEQUENCE. MODELS 16-27 OF A 27-MODEL SET.
