Platelet factor 4

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Orthologs
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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.

Genomics

The gene for human PF4 is located on human chromosome 4.[2]

Function

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]

PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3B.[4]

Clinical significance

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]

It is increased in patients with systemic sclerosis that also have interstitial lung disease.[7]

The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.[8]

See also

References

  1. 1.0 1.1 Eisman 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. PMID 1695112.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  2. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  3. "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)".<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  4. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  5. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  7. Volkmann ER, Tashkin DP, Roth MD, Clements PJ, Khanna D, Furst DE, Mayes M, Charles J, Tseng CH, Elashoff RM, Assassi S (2016). "Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease" (PDF). Arthritis Research & Therapy. 18: 305. doi:10.1186/s13075-016-1203-y.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  8. 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. PMID 23245326.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

Further reading

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  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Nath N, Lowery CT, Niewiarowski S (1975). "Antigenic and antiheparin properties of human platelet factor 4 (PF4)". Blood. 45 (4): 537–50. PMID 803847.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Morgan FJ, Begg GS, Chesterman CN (1980). "Complete covalent structure of human platelet factor 4". Thromb. Haemost. 42 (5): 1652–60. PMID 6445090.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.