Platelet factor 4 (PF4) is a smallcytokine belonging to the CXCchemokine family that is also known aschemokine (C-X-C motif) ligand 4 (CXCL4) . This chemokine is released fromalpha-granules of activatedplatelets during platelet aggregation, and promotes bloodcoagulation by moderating the effects ofheparin-like molecules. Due to these roles, it is predicted to play a role inwound repair andinflammation.[5] It is usually found in a complex withproteoglycan.
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 localantithrombin activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair.[5][7]
There are a set of prothrombotic conditions caused by monoclonal antibodies against Platelet factor 4 (anti-PF4) that presents with recurrent thrombosis and persistent thrombocytopenia.[9][10] At least one author has called theseMonoclonal gammopathy of thrombotic significance.
The heparin:PF4 complex is the antigen inheparin-induced thrombocytopenia (HIT), an idiosyncratic autoimmune reaction to the administration of the anticoagulantheparin.[11] PF4autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.[12]
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^Warkentin TE (March 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis".The New England Journal of Medicine.356 (9):891–893.doi:10.1056/NEJMp068309.PMID17329695.
^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):632–636.doi:10.1016/j.amjmed.2008.03.012.PMID18589060.
Bikfalvi A, Gimenez-Gallego G (February 2004). "The control of angiogenesis and tumor invasion by platelet factor-4 and platelet factor-4-derived molecules".Seminars in Thrombosis and Hemostasis.30 (1):137–44.doi:10.1055/s-2004-822978.PMID15034805.S2CID260320397.
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.PMID601757.
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.PMID1688470.
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.PMID2140694.S2CID24529258.
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.PMID3622011.
Morgan FJ, Begg GS, Chesterman CN (February 1980). "Complete covalent structure of human platelet factor 4".Thrombosis and Haemostasis.42 (5):1652–60.PMID6445090.
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.PMID8031770.
Horne MK (April 1993). "The effect of secreted heparin-binding proteins on heparin binding to platelets".Thrombosis Research.70 (1):91–8.doi:10.1016/0049-3848(93)90226-E.PMID8511754.
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.PMID8613703.S2CID23125881.
1f9r: CRYSTAL STRUCTURE OF PLATELET FACTOR 4 MUTANT 1
1f9s: CRYSTAL STRUCTURE OF PLATELET FACTOR 4 MUTANT 2
1pfm: PF4-M2 CHIMERIC MUTANT WITH THE FIRST 10 N-TERMINAL RESIDUES OF R-PF4 REPLACED BY THE N-TERMINAL RESIDUES OF THE IL8 SEQUENCE. MODELS 1-15 OF A 27-MODEL SET.
1pfn: PF4-M2 CHIMERIC MUTANT WITH THE FIRST 10 N-TERMINAL RESIDUES OF R-PF4 REPLACED BY THE N-TERMINAL RESIDUES OF THE IL8 SEQUENCE. MODELS 16-27 OF A 27-MODEL SET.
1rhp: CRYSTAL STRUCTURE OF RECOMBINANT HUMAN PLATELET FACTOR 4
