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

PF4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPF4, CXCL4, PF-4, SCYB4, platelet factor 4
External IDsOMIM: 173460 MGI: 1888711 HomoloGene: 87791 GeneCards: PF4
Orthologs
SpeciesHumanMouse
Entrez

5196

56744

Ensembl

ENSG00000163737

ENSMUSG00000029373

UniProt

P02776

Q9Z126

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: 90.92 – 90.92 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Genomics

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

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 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 CXCR3-B.[8]

Clinical significance

The heparin:PF4 complex is the antigen in heparin-induced thrombocytopenia (HIT), 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] Antibodies against PF4 have been implicated in cases of thrombosis and thrombocytopenia subsequent to vaccination with the Oxford–AstraZeneca or the Janssen COVID-19 vaccine.[11][12] This phenomenon has been termed vaccine-induced immune thrombotic thrombocytopenia (VITT).[13] Changes in the expression of PF4 have also been associated with symptoms of long COVID.[14]

It is increased in patients with systemic sclerosis that also have interstitial lung disease.[15]

The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.[16]

See also

References

  1. GRCh38: Ensembl release 89: ENSG00000163737 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000029373 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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. doi:10.1182/blood.V76.2.336.336. PMID 1695112.
  6. O'Donovan N, Galvin M, Morgan JG (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenetics and Cell Genetics. 84 (1–2): 39–42. doi:10.1159/000015209. PMID 10343098. S2CID 8087808.
  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, et al. (June 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". The Journal of Experimental Medicine. 197 (11): 1537–49. doi:10.1084/jem.20021897. PMC 2193908. PMID 12782716.
  9. Warkentin TE (March 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". The New England Journal of Medicine. 356 (9): 891–3. 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". The American Journal of Medicine. 121 (7): 632–6. doi:10.1016/j.amjmed.2008.03.012. PMID 18589060.
  11. Schultz NH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, et al. (April 2021). "Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination". The New England Journal of Medicine. 384 (22): 2124–2130. doi:10.1056/NEJMoa2104882. ISSN 0028-4793. PMC 8112568. PMID 33835768.
  12. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S (April 2021). "Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination". The New England Journal of Medicine. 384 (22): 2092–2101. doi:10.1056/NEJMoa2104840. PMC 8095372. PMID 33835769.
  13. Arepally GM, Ortel TL (June 2021). "Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): What We Know and Don't Know". Blood. doi:10.1182/blood.2021012152. PMC 8172307. PMID 34061166.
  14. Ryan FJ, Hope CM, Masavuli MG, Lynn MA, Mekonnen ZA, Yeow AE, et al. (January 2022). "Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection". BMC Medicine. 20 (1): 26. doi:10.1186/s12916-021-02228-6. PMC 8758383. PMID 35027067.
  15. Volkmann ER, Tashkin DP, Roth MD, Clements PJ, Khanna D, Furst DE, et al. (December 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". Arthritis Research & Therapy. 18 (1): 305. doi:10.1186/s13075-016-1203-y. PMC 5203703. PMID 28038680.
  16. Love MS, Millholland MG, Mishra S, Kulkarni S, Freeman KB, Pan W, et al. (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. PMC 3638032. PMID 23245326.

Further reading

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