Platelet factor 4
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.
PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3B.[2] The gene for human PF4 is located on human chromosome 4.[3]
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 (Eisman et al., 1990).[supplied by OMIM][4]
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]
References
- ^ Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M (1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood 76 (2): 336–44. PMID 1695112.
- ^ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (2003). "An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4". J Exp Med 197 (11): 1537–1549. doi:10.1084/jem.20021897. PMC 2193908. PMID 12782716. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2193908.
- ^ 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. PMID 10343098.
- ^ "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5196.
- ^ Warkentin TE (March 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". N. Engl. J. Med. 356 (9): 891–893. doi:10.1056/NEJMp068309. PMID 17329695. http://content.nejm.org/cgi/content/full/356/9/891.
- ^ Warkentin TE, Makris M, Jay RM, Kelton JG (July 2008). "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". Am. J. Med. 121 (7): 632–636. doi:10.1016/j.amjmed.2008.03.012. PMID 18589060.
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. PMID 15034805.
- 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. PMID 17381065.
- Deuel TF, Keim PS, Farmer M, Heinrikson RL (1977). "Amino acid sequence of human platelet factor 4". Proc. Natl. Acad. Sci. U.S.A. 74 (6): 2256–2258. doi:10.1073/pnas.74.6.2256. PMC 432148. PMID 267922. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=432148.
- 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. PMID 601757.
- Nath N, Lowery CT, Niewiarowski S (1975). "Antigenic and antiheparin properties of human platelet factor 4 (PF4)". Blood 45 (4): 537–50. PMID 803847.
- 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. PMID 893407.
- 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. PMID 1688470.
- Eisman R, Surrey S, Ramachandran B et al. (1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood 76 (2): 336–44. PMID 1695112.
- 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. PMID 2140694.
- 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. PMID 3098319.
- 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. PMID 3622011.
- Senior RM, Griffin GL, Huang JS et al. (1983). "Chemotactic activity of platelet alpha granule proteins for fibroblasts". J. Cell Biol. 96 (2): 382–385. doi:10.1083/jcb.96.2.382. PMC 2112304. PMID 6187750. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2112304.
- Morgan FJ, Begg GS, Chesterman CN (1980). "Complete covalent structure of human platelet factor 4". Thromb. Haemost. 42 (5): 1652–60. PMID 6445090.
- Deuel TF, Senior RM, Chang D et al. (1981). "Platelet factor 4 is chemotactic for neutrophils and monocytes". Proc. Natl. Acad. Sci. U.S.A. 78 (7): 4584–4587. doi:10.1073/pnas.78.7.4584. PMC 319837. PMID 6945600. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=319837.
- 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. PMID 7524669.
- 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. PMID 7547867.
- 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. PMID 7835432.
- 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. PMID 8031770.
- 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. PMID 8511754.
- 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. PMID 8613703.
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PDB gallery
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1f9q: CRYSTAL STRUCTURE OF PLATELET FACTOR 4
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1f9r: CRYSTAL STRUCTURE OF PLATELET FACTOR 4 MUTANT 1
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1f9s: CRYSTAL STRUCTURE OF PLATELET FACTOR 4 MUTANT 2
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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.
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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.
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1rhp: CRYSTAL STRUCTURE OF RECOMBINANT HUMAN PLATELET FACTOR 4
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See also
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IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21, IFNB1, IFNK, IFNW1
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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biochemical families: prot · nucl · carb (glpr, alco, glys) · lipd (fata/i, phld, strd, gllp, eico) · amac/i · ncbs/i · ttpy/i
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.