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.
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The gene for human PF4 is located on human chromosome 4.[6]
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]
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]
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- Walz DA, Wu VY, de Lamo R, Dene H, McCoy LE (December 1977). "Primary structure of human platelet factor 4". Thrombosis Research. 11 (6): 893–8. doi:10.1016/0049-3848(77)90117-7. PMID 601757.
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- Maione TE, Gray GS, Petro J, Hunt AJ, Donner AL, Bauer SI, et al. (January 1990). "Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides". Science. 247 (4938): 77–9. Bibcode:1990Sci...247...77M. doi:10.1126/science.1688470. PMID 1688470.
- Han ZC, Bellucci S, Tenza D, Caen JP (April 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". British Journal of Haematology. 74 (4): 395–401. doi:10.1111/j.1365-2141.1990.tb06325.x. PMID 2140694. S2CID 24529258.
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- Griffin CA, Emanuel BS, LaRocco P, Schwartz E, Poncz M (1987). "Human platelet factor 4 gene is mapped to 4q12----q21". Cytogenetics and Cell Genetics. 45 (2): 67–9. doi:10.1159/000132431. PMID 3622011.
- Senior RM, Griffin GL, Huang JS, Walz DA, Deuel TF (February 1983). "Chemotactic activity of platelet alpha granule proteins for fibroblasts". The Journal of Cell Biology. 96 (2): 382–5. doi:10.1083/jcb.96.2.382. PMC 2112304. PMID 6187750.
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- Brown KJ, Parish CR (November 1994). "Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor". Biochemistry. 33 (46): 13918–27. doi:10.1021/bi00250a047. PMID 7524669.
- Mayo KH, Roongta V, Ilyina E, Milius R, Barker S, Quinlan C, et al. (September 1995). "NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N-terminal chimera: a symmetric tetramer". Biochemistry. 34 (36): 11399–409. doi:10.1021/bi00036a012. PMID 7547867.
- Barker S, Mayo KH (January 1995). "Quarternary structure amplification of protein folding differences observed in 'native' platelet factor-4". FEBS Letters. 357 (3): 301–4. Bibcode:1995FEBSL.357..301B. doi:10.1016/0014-5793(94)01384-D. PMID 7835432. S2CID 12222261.
- Zhang X, Chen L, Bancroft DP, Lai CK, Maione TE (July 1994). "Crystal structure of recombinant human platelet factor 4". Biochemistry. 33 (27): 8361–6. doi:10.1021/bi00193a025. PMID 8031770.
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- Kolset SO, Mann DM, Uhlin-Hansen L, Winberg JO, Ruoslahti E (April 1996). "Serglycin-binding proteins in activated macrophages and platelets". Journal of Leukocyte Biology. 59 (4): 545–54. doi:10.1002/jlb.59.4.545. PMID 8613703. S2CID 23125881.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.