Factor plaquetario 4

PF4
Estruturas dispoñibles
PDB	Buscar ortólogos: PDBe, RCSB Lista de códigos PDB 1RHP, 1DN3, 1F9Q, 1F9R, 1F9S, 1PFM, 1PFN, 4R9W, 4R9Y, 4RAU ;
Identificadores
Símbolos	PF4 (HGNC: 8861) CXCL4, PF-4, SCYB4, factor plaquetario 4
Identificadores; externos	OMIM: 173460 ; MGI: 1888711 ; HomoloGene: 87791 ; EBI: PF4; GeneCards: Xene PF4; UniProt: PF4;
Locus	Cr. 4 q13.3
Ontoloxía Xénica	Referencias: AmiGO / QuickGO
	Referencias: AmiGO / QuickGO
Padrón de expresión de ARNm
	Máis información
Estrutura/Función proteica
Tamaño	70 (aminoácidos)
Ortólogos
Especies
Humano	Rato
Entrez
5196	56744
Ensembl
Véxase HS	Véxase MM
UniProt
P02776	Q9Z126
RefSeq; (ARNm)
NM_002619	NM_019932
RefSeq; (proteína) NCBI
NP_002610	NP_064316
Localización (UCSC)
Cr. 4:; 73.98 – 73.98 Mb	Cr. 5:; 90.77 – 90.77 Mb
PubMed (Busca)
5196 ;	56744

O factor plaquetario 4 (PF4) é unha pequena citocina que pertence á familia das quimiocinas CXC que tamén se coñece como quimiocina (motivo C-X-C) ligando 4 (CXCL4) . Esta quimiocina é liberada dos gránulos alfa das plaquetas activadas durante a agregación plaquetaria e promove a coagulación do sangue ao moderar os efectos das moléculas similares á heparina. Debido a estas funcións, prediciuse que desempeña un papel na reparación de feridas e na inflamación.^[1] Xeralmente atópase formando un complexo cun proteoglicano.

Xenómicas

O xene que codifica o PF4 humano está localizado no cromosoma 4.^[2]

Función

O factor plaquetario 4 é unha proteína de 70 aminoácidos que se libera dos gránulos alfa de plaquetas activadas e únese con alta afinidade á heparina. O seu principal papel fisiolóxico parece ser a neutralización de moléculas similares á heparina da superficie endotelial dos vasos sanguíneos, inhibindo a actividade da antitrombina III local e promovendo a coagulación. Como forte quimioatractor para os neutrófilos e fibroblastos, o PF4 probablemente exerce un papel na inflamación e reparación de feridas.^[1]^[3]

O PF4 é quimotáctico para os neutrófilos, fibroblastos e monocitos e interacciona cunha variante de empalme do receptor da quimocina CXCR3, coñecida como CXCR3B.^[4]

Importancia clínica

O complexo heparina:PF4 é o antíxeno na trombocitopenia inducida por heparina, unha reacción autoinmune idiosincrática á administración de heparina anticoagulante.^[5] Os autoanticorpos anti-PF4 tamén se encontraron en pacientes con trombose e características que lembran a trombocitopenia inducida por heparina pero non antes da administración de heparina.^[6]

Os niveis de PF4 increméntanse en pacientes con esclerose sistémica que tamén teñen enfermidade pulmonar intersticial.^[7]

O PF4 humano mata os parasitos da malaria dentro dos eritrocitos ao lisar selectivamente os vacúolos dixestivos do parasito.^[8]

Notas

↑ ^1,0 ^1,1 Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M (xullo de 1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood 76 (2): 336–44. PMID 1695112.
↑ 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. PMID 10343098. doi:10.1159/000015209.
↑ "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 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. PMC 2193908. PMID 12782716. doi:10.1084/jem.20021897.
↑ Warkentin TE (marzo de 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". N. Engl. J. Med. 356 (9): 891–893. PMID 17329695. doi:10.1056/NEJMp068309. Arquivado dende o orixinal o 28 de marzo de 2007. Consultado o 23 de setembro de 2018.
↑ Warkentin TE, Makris M, Jay RM, Kelton JG (xullo de 2008). "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". Am. J. Med. 121 (7): 632–636. PMID 18589060. doi:10.1016/j.amjmed.2008.03.012.
↑ 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.
↑ 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 (decembro de 2012). "Platelet Factor 4 Activity against P. falciparum and Its Translation to Nonpeptidic Mimics as Antimalarials". Cell Host Microbe 12 (6): 815–23. PMID 23245326. doi:10.1016/j.chom.2012.10.017.

Véxase tamén

Outros artigos

Bibliografía

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. PMID 15034805. doi:10.1055/s-2004-822978.
Maurer AM, Zhou B, Han ZC (2007). "Roles of platelet factor 4 in hematopoiesis and angiogenesis". Growth Factors 24 (4): 242–252. PMID 17381065. doi:10.1080/08977190600988225.
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. PMC 432148. PMID 267922. doi:10.1073/pnas.74.6.2256.
Walz DA, Wu VY, de Lamo R, et al. (1978). "Primary structure of human platelet factor 4". Thromb. Res. 11 (6): 893–898. PMID 601757. doi:10.1016/0049-3848(77)90117-7.
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. PMID 1688470. doi:10.1126/science.1688470.
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. PMID 2140694. doi:10.1111/j.1365-2141.1990.tb06325.x.
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. PMID 3622011. doi:10.1159/000132431.
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. PMC 2112304. PMID 6187750. doi:10.1083/jcb.96.2.382.
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. PMC 319837. PMID 6945600. doi:10.1073/pnas.78.7.4584.
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. PMID 7524669. doi:10.1021/bi00250a047.
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. PMID 7547867. doi:10.1021/bi00036a012.
Barker S, Mayo KH (1995). "Quarternary structure amplification of protein folding differences observed in 'native' platelet factor-4". FEBS Lett. 357 (3): 301–304. PMID 7835432. doi:10.1016/0014-5793(94)01384-D.
Zhang X, Chen L, Bancroft DP, et al. (1994). "Crystal structure of recombinant human platelet factor 4". Biochemistry 33 (27): 8361–8366. PMID 8031770. doi:10.1021/bi00193a025.
Horne MK (1993). "The effect of secreted heparin-binding proteins on heparin binding to platelets". Thromb. Res. 70 (1): 91–98. PMID 8511754. doi:10.1016/0049-3848(93)90226-E.
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.

Ligazóns externas

Platelet factor 4 Medical Subject Headings (MeSH) na Biblioteca Nacional de Medicina dos EUA.

Este artigo incorpora textos da Biblioteca Nacional de Medicina dos Estados Unidos, en dominio público.

[Eisman_1990-1] 1,0 ^1,1 Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M (xullo de 1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood 76 (2): 336–44. PMID 1695112.

[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. PMID 10343098. doi:10.1159/000015209.

[3] "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)".

[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. PMC 2193908. PMID 12782716. doi:10.1084/jem.20021897.

[5] Warkentin TE (marzo de 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". N. Engl. J. Med. 356 (9): 891–893. PMID 17329695. doi:10.1056/NEJMp068309. Arquivado dende o orixinal o 28 de marzo de 2007. Consultado o 23 de setembro de 2018.

[6] Warkentin TE, Makris M, Jay RM, Kelton JG (xullo de 2008). "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". Am. J. Med. 121 (7): 632–636. PMID 18589060. doi:10.1016/j.amjmed.2008.03.012.

[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.

[pmid23245326-8] 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 (decembro de 2012). "Platelet Factor 4 Activity against P. falciparum and Its Translation to Nonpeptidic Mimics as Antimalarials". Cell Host Microbe 12 (6): 815–23. PMID 23245326. doi:10.1016/j.chom.2012.10.017.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]