Platelet factor 4

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PF4
Protein PF4 PDB 1f9q.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPF4, CXCL4, PF-4, SCYB4, platelet factor 4
External IDsOMIM: 173460 MGI: 1888711 HomoloGene: 87791 GeneCards: PF4
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for PF4
Genomic location for PF4
Band4q13.3Start73,981,077 bp[1]
End73,982,124 bp[1]
RNA expression pattern
PBB GE PF4 206390 x at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002619
NM_001363352

NM_019932

RefSeq (protein)

NP_002610
NP_001350281

NP_064316

Location (UCSC)Chr 4: 73.98 – 73.98 MbChr 5: 90.77 – 90.77 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] It is usually found in a complex with proteoglycan.

Genomics[edit]

The gene for human PF4 is located on human chromosome 4.[6]

Function[edit]

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.[5][7]

PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3B.[8]

Clinical significance[edit]

The heparin:PF4 complex is the antigen in heparin-induced thrombocytopenia, an idiosyncratic autoimmune reaction to the administration of the anticoagulant heparin.[9] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.[10]

It is increased in patients with systemic sclerosis that also have interstitial lung disease.[11]

The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.[12]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163737 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029373 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ a b 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.
  6. ^ 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.
  7. ^ "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)".
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.

Further reading[edit]

External links[edit]

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