Factor plaquetario 4: Diferenzas entre revisións

O '''factor plaquetario 4''' (PF4) é unha pequena [[citocina]] que pertence á familia das [[quimiocina]]s CXC que tamén se coñece como '''quimiocina (motivo C-X-C) ligando 4''' (CXCL4) . Esta quimiocina é liberada dos [[gránulo alfa das plaquetas|gránulos alfa]] das [[plaqueta]]s 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]].<ref name="Eisman_1990">{{citeCita journalpublicación periódica |vauthors=Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M | title = Structural and functional comparison of the genes for human platelet factor 4 and PF4alt | journal = Blood | volume = 76 | issue = 2 | pages = 336–44 |date=July 1990 | pmid = 1695112 | doi = }}</ref> Xeralmente atópase formando un complexo cun [[proteoglicano]].

O [[xene]] que codifica o PF4 humano está localizado no [[cromosoma 4]].<ref>{{citeCita journalpublicación periódica |vauthors=O'Donovan N, Galvin M, Morgan J |title=Physical mapping of the CXC chemokine locus on human chromosome 4 |journal=Cytogenet Cell Genet |volume=84 |issue=1–2 |pages=39–42 |year=1999 |pmid=10343098 |doi=10.1159/000015209}}</ref>

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 [[endotelio|endotelial]] dos [[vaso sanguíneo|vasos sanguíneos]], inhibindo a actividade da [[antitrombina III]] local e promovendo a coagulación. Como forte quimioatractor para os [[neutrófilo]]s e [[fibroblasto]]s, o PF4 probablemente exerce un papel na inflamación e reparación de feridas.<ref name="Eisman_1990"/><ref>{{citeCita web | title = Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5196| accessdate = }}</ref>

O PF4 é quimotáctico para os neutrófilos, fibroblastos e [[monocito]]s e interacciona cunha [[empalme alternativo|variante de empalme]] do receptor da quimocina [[receeptores da quimocina CXC|CXCR3]], coñecido como CXCR3B.<ref>{{citeCita journalpublicación periódica |vauthors=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 |title=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 |journal=J Exp Med |volume=197 |issue=11 |pages=1537–1549 |year=2003 |pmid=12782716 |doi=10.1084/jem.20021897 |pmc=2193908}}</ref>

O complexo heparina:PF4 é o [[antíxeno]] na [[trombocitopenia inducida por heparina]], unha reacción [[autoinmunidade|autoinmune]] idiosincrática á administración de heparina anticoagulante.<ref>{{citeCita journalpublicación periódica |author=Warkentin TE |title=Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis |journal=N. Engl. J. Med. |volume=356 |issue=9 |pages=891–893 |date=March 2007 |pmid=17329695 |doi=10.1056/NEJMp068309 |url=http://content.nejm.org/cgi/content/full/356/9/891}}</ref> Os [[autoanticorpo]]s 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.<ref>{{citeCita journalpublicación periódica |vauthors=Warkentin TE, Makris M, Jay RM, Kelton JG |title=A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia |journal=Am. J. Med. |volume=121 |issue=7 |pages=632–636 |date=July 2008 |pmid=18589060 |doi=10.1016/j.amjmed.2008.03.012}}</ref>

Os niveis de PF4 increméntanse en pacientes con [[esclerose sistémica]] que tamén teñen [[enfermidade pulmonar intersticial]].<ref>{{citeCita journalpublicación periódica | vauthors=Volkmann ER, Tashkin DP, Roth MD, Clements PJ, Khanna D, Furst DE, Mayes M, Charles J, Tseng CH, Elashoff RM, Assassi S | title = Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203703/pdf/13075_2016_Article_1203.pdf | journal = Arthritis Research & Therapy | volume = 18 | pages = 305 | date= 2016 |doi = 10.1186/s13075-016-1203-y }}</ref>

O PF4 humano mata os [[Plasmodium|parasitos da malaria]] dentro dos [[eritrocito]]s ao lisar selectivamente os [[vacúolo]]s dixestivos do parasito.<ref name="pmid23245326">{{citeCita journalpublicación periódica |vauthors=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 | title = Platelet Factor 4 Activity against P. falciparum and Its Translation to Nonpeptidic Mimics as Antimalarials | journal = Cell Host Microbe | volume = 12 | issue = 6 | pages = 815–23 | date=December 2012 | pmid = 23245326 | doi = 10.1016/j.chom.2012.10.017 }}</ref>

*{{citeCita journalpublicación periódica |vauthors=Bikfalvi A, Gimenez-Gallego G |title=The control of angiogenesis and tumor invasion by platelet factor-4 and platelet factor-4-derived molecules |journal=Semin. Thromb. Hemost. |volume=30 |issue= 1 |pages= 137–144 |year= 2004 |pmid= 15034805 |doi= 10.1055/s-2004-822978 }}

*{{citeCita journalpublicación periódica |vauthors=Maurer AM, Zhou B, Han ZC |title=Roles of platelet factor 4 in hematopoiesis and angiogenesis |journal=Growth Factors |volume=24 |issue= 4 |pages= 242–252 |year= 2007 |pmid= 17381065 |doi=10.1080/08977190600988225 }}

*{{citeCita journalpublicación periódica |vauthors=Deuel TF, Keim PS, Farmer M, Heinrikson RL |title=Amino acid sequence of human platelet factor 4 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=74 |issue= 6 |pages= 2256–2258 |year= 1977 |pmid= 267922 |doi=10.1073/pnas.74.6.2256 | pmc=432148 }}

*{{citeCita journalpublicación periódica | author=Walz DA |title=Primary structure of human platelet factor 4 |journal=Thromb. Res. |volume=11 |issue= 6 |pages= 893–898 |year= 1978 |pmid= 601757 |doi=10.1016/0049-3848(77)90117-7 |name-list-format=vanc| author2=Wu VY | author3=de Lamo R | display-authors=3 | last4=Dene | first4=Howard | last5=McCoy | first5=Lowell E }}

*{{citeCita journalpublicación periódica |vauthors=Nath N, Lowery CT, Niewiarowski S |title=Antigenic and antiheparin properties of human platelet factor 4 (PF4) |journal=Blood |volume=45 |issue= 4 |pages= 537–50 |year= 1975 |pmid= 803847 |doi= }}

*{{citeCita journalpublicación periódica |vauthors=Hermodson M, Schmer G, Kurachi K |title=Isolation, crystallization, and primary amino acid sequence of human platelet factor 4 |journal=J. Biol. Chem. |volume=252 |issue= 18 |pages= 6276–9 |year= 1977 |pmid= 893407 |doi= }}

*{{citeCita journalpublicación periódica | author=Maione TE |title=Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides |journal=Science |volume=247 |issue= 4938 |pages= 77–79 |year= 1990 |pmid= 1688470 |doi=10.1126/science.1688470 |name-list-format=vanc| author2=Gray GS | author3=Petro J | display-authors=3 | last4=Hunt | first4=A. | last5=Donner | first5=A. | last6=Bauer | first6=S. | last7=Carson | first7=H. | last8=Sharpe | first8=R. }}

*{{citeCita journalpublicación periódica |vauthors=Han ZC, Bellucci S, Tenza D, Caen JP |title=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 |journal=Br. J. Haematol. |volume=74 |issue= 4 |pages= 395–401 |year= 1990 |pmid= 2140694 |doi=10.1111/j.1365-2141.1990.tb06325.x }}

*{{citeCita journalpublicación periódica | author=Poncz M |title=Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line |journal=Blood |volume=69 |issue= 1 |pages= 219–23 |year= 1987 |pmid= 3098319 |doi= |name-list-format=vanc| author2=Surrey S | author3=LaRocco P | display-authors=3 | last4=Weiss | first4=MJ | last5=Rappaport | first5=EF | last6=Conway | first6=TM | last7=Schwartz | first7=E }}

*{{citeCita journalpublicación periódica | author=Griffin CA |title=Human platelet factor 4 gene is mapped to 4q12----q21 |journal=Cytogenet. Cell Genet. |volume=45 |issue= 2 |pages= 67–69 |year= 1987 |pmid= 3622011 |doi=10.1159/000132431 |name-list-format=vanc| author2=Emanuel BS | author3=LaRocco P | display-authors=3 | last4=Schwartz | first4=E. | last5=Poncz | first5=M. }}

*{{citeCita journalpublicación periódica | author=Senior RM |title=Chemotactic activity of platelet alpha granule proteins for fibroblasts |journal=J. Cell Biol. |volume=96 |issue= 2 |pages= 382–385 |year= 1983 |pmid= 6187750 |doi=10.1083/jcb.96.2.382 | pmc=2112304 |name-list-format=vanc| author2=Griffin GL | author3=Huang JS | display-authors=3 | last4=Walz | first4=DA | last5=Deuel | first5=TF }}

*{{citeCita journalpublicación periódica |vauthors=Morgan FJ, Begg GS, Chesterman CN |title=Complete covalent structure of human platelet factor 4 |journal=Thromb. Haemost. |volume=42 |issue= 5 |pages= 1652–60 |year= 1980 |pmid= 6445090 |doi= }}

*{{citeCita journalpublicación periódica | author=Deuel TF |title=Platelet factor 4 is chemotactic for neutrophils and monocytes |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=78 |issue= 7 |pages= 4584–4587 |year= 1981 |pmid= 6945600 |doi=10.1073/pnas.78.7.4584 | pmc=319837 |name-list-format=vanc| author2=Senior RM | author3=Chang D | display-authors=3 | last4=Griffin | first4=GL | last5=Heinrikson | first5=RL | last6=Kaiser | first6=ET }}

*{{citeCita journalpublicación periódica |vauthors=Brown KJ, Parish CR |title=Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor |journal=Biochemistry |volume=33 |issue= 46 |pages= 13918–13927 |year= 1994 |pmid= 7524669 |doi=10.1021/bi00250a047 }}

*{{citeCita journalpublicación periódica | author=Mayo KH |title=NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N-terminal chimera: a symmetric tetramer |journal=Biochemistry |volume=34 |issue= 36 |pages= 11399–11409 |year= 1995 |pmid= 7547867 |doi=10.1021/bi00036a012 |name-list-format=vanc| author2=Roongta V | author3=Ilyina E | display-authors=3 | last4=Milius | first4=Robert | last5=Barker | first5=Sharon | last6=Quinlan | first6=Christopher | last7=La Rosa | first7=Greg | last8=Daly | first8=Thomas J. }}

*{{citeCita journalpublicación periódica |vauthors=Barker S, Mayo KH |title=Quarternary structure amplification of protein folding differences observed in 'native' platelet factor-4 |journal=FEBS Lett. |volume=357 |issue= 3 |pages= 301–304 |year= 1995 |pmid= 7835432 |doi=10.1016/0014-5793(94)01384-D }}

*{{citeCita journalpublicación periódica | author=Zhang X |title=Crystal structure of recombinant human platelet factor 4 |journal=Biochemistry |volume=33 |issue= 27 |pages= 8361–8366 |year= 1994 |pmid= 8031770 |doi=10.1021/bi00193a025 |name-list-format=vanc| author2=Chen L | author3=Bancroft DP | display-authors=3 | last4=Lai | first4=C. K. | last5=Maione | first5=Theodore E. }}

*{{citeCita journalpublicación periódica | author=Horne MK |title=The effect of secreted heparin-binding proteins on heparin binding to platelets |journal=Thromb. Res. |volume=70 |issue= 1 |pages= 91–98 |year= 1993 |pmid= 8511754 |doi=10.1016/0049-3848(93)90226-E }}

*{{citeCita journalpublicación periódica | author=Kolset SO |title=Serglycin-binding proteins in activated macrophages and platelets |journal=J. Leukoc. Biol. |volume=59 |issue= 4 |pages= 545–54 |year= 1996 |pmid= 8613703 |doi= |name-list-format=vanc| author2=Mann DM | author3=Uhlin-Hansen L | display-authors=3 | last4=Winberg | first4=JO | last5=Ruoslahti | first5=E }}