Biology:Platelet factor 4

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Short description: Protein involved in blood clotting, wound healing and inflammation


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


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 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 CXCR3-B.[4]

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.[5] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.[6] 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.[7][8] This phenomenon has been termed vaccine-induced immune thrombotic thrombocytopenia (VITT).[9] Changes in the expression of PF4 have also been associated with symptoms of long COVID.[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

References

  1. ↑ 1.0 1.1 "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood 76 (2): 336–44. July 1990. doi:10.1182/blood.V76.2.336.336. PMID 1695112. 
  2. ↑ "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenetics and Cell Genetics 84 (1–2): 39–42. 1999. doi:10.1159/000015209. PMID 10343098. 
  3. ↑ "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5196. 
  4. ↑ "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. June 2003. doi:10.1084/jem.20021897. PMID 12782716. 
  5. ↑ "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". The New England Journal of Medicine 356 (9): 891–3. March 2007. doi:10.1056/NEJMp068309. PMID 17329695. 
  6. ↑ "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". The American Journal of Medicine 121 (7): 632–6. July 2008. doi:10.1016/j.amjmed.2008.03.012. PMID 18589060. 
  7. ↑ "Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination". The New England Journal of Medicine 384 (22): 2124–2130. April 2021. doi:10.1056/NEJMoa2104882. ISSN 0028-4793. PMID 33835768. 
  8. ↑ "Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination". The New England Journal of Medicine 384 (22): 2092–2101. April 2021. doi:10.1056/NEJMoa2104840. PMID 33835769. 
  9. ↑ "Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): What We Know and Don't Know". Blood. June 2021. doi:10.1182/blood.2021012152. PMID 34061166. 
  10. ↑ "Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection". BMC Medicine 20 (1): 26. January 2022. doi:10.1186/s12916-021-02228-6. PMID 35027067. 
  11. ↑ "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. December 2016. doi:10.1186/s13075-016-1203-y. PMID 28038680. 
  12. ↑ "Platelet factor 4 activity against P. falciparum and its translation to nonpeptidic mimics as antimalarials". Cell Host & Microbe 12 (6): 815–23. December 2012. doi:10.1016/j.chom.2012.10.017. PMID 23245326. 

Further reading

External links

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



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