platelet factor 4


Gene Symbol: platelet factor 4
Description: platelet factor 4
Alias: Cxcl4, Scyb4, platelet factor 4, C-X-C motif chemokine 4, PF-4, chemokine (C-X-C motif) ligand 4
Species: mouse
Products:     platelet factor 4

Top Publications

  1. Eslin D, Zhang C, Samuels K, Rauova L, Zhai L, Niewiarowski S, et al. Transgenic mice studies demonstrate a role for platelet factor 4 in thrombosis: dissociation between anticoagulant and antithrombotic effect of heparin. Blood. 2004;104:3173-80 pubmed
    The platelet-specific chemokine platelet factor 4 (PF4) is released in large amounts at sites of vascular injury. PF4 binds to heparin with high affinity, but its in vivo biologic role has not been defined...
  2. Lambert M, Rauova L, Bailey M, Sola Visner M, Kowalska M, Poncz M. Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications. Blood. 2007;110:1153-60 pubmed
    b>Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis in vitro. We have now examined whether PF4 regulates megakaryopoiesis in vivo by studying PF4 knockout mice and transgenic mice that overexpress human (h) PF4...
  3. Cervi D, Yip T, Bhattacharya N, Podust V, Peterson J, Abou Slaybi A, et al. Platelet-associated PF-4 as a biomarker of early tumor growth. Blood. 2008;111:1201-7 pubmed
    ..We conclude that platelet-associated PF-4, but not its plasma counterpart, may represent a potential biomarker of early tumor presence. ..
  4. Kowalska M, Mahmud S, Lambert M, Poncz M, Slungaard A. Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge. Blood. 2007;110:1903-5 pubmed
    Pharmacologic infusion of activated protein C (APC) improves survival in severe sepsis, and platelet factor 4 (PF4) accelerates APC generation in a primate thrombin-infusion model...
  5. Srivastava K, Cockburn I, Swaim A, Thompson L, Tripathi A, Fletcher C, et al. Platelet factor 4 mediates inflammation in experimental cerebral malaria. Cell Host Microbe. 2008;4:179-87 pubmed publisher
    ..We now demonstrate that the platelet-derived chemokine, platelet factor 4 (PF4)/CXCL4, promotes the development of experimental cerebral malaria (ECM)...
  6. Sachais B, Turrentine T, Dawicki McKenna J, Rux A, Rader D, Kowalska M. Elimination of platelet factor 4 (PF4) from platelets reduces atherosclerosis in C57Bl/6 and apoE-/- mice. Thromb Haemost. 2007;98:1108-13 pubmed
    Activated platelets, which release platelet factor 4 (PF4) are present in patients with atherosclerosis. To date, no direct in-vivo evidence exists for the involvement of PF4 in atherogenesis...
  7. Wilson G, Hewit K, Pallas K, Cairney C, Lee K, Hansell C, et al. Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland. Development. 2017;144:74-82 pubmed publisher
    ..These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes. ..
  8. Rampon C, Huber P. Multilineage hematopoietic progenitor activity generated autonomously in the mouse yolk sac: analysis using angiogenesis-defective embryos. Int J Dev Biol. 2003;47:273-80 pubmed
    ..The small number of definitive mature blood cells indicates however that the yolk sac is not an effective environment for the terminal differentiation of committed progenitors from the second wave of hematopoiesis. ..
  9. Rue L, Bañez Coronel M, Creus Muncunill J, Giralt A, Alcalá Vida R, Mentxaka G, et al. Targeting CAG repeat RNAs reduces Huntington's disease phenotype independently of huntingtin levels. J Clin Invest. 2016;126:4319-4330 pubmed publisher

More Information


  1. Guo H, Wang Y, Zhao Z, Shao X. Platelet factor 4 limits Th17 differentiation and ischaemia-reperfusion injury after liver transplantation in mice. Scand J Immunol. 2015;81:129-34 pubmed publisher
    ..b>Platelet factor 4 (PF4) was the first discovered CXC chemokine and is found in platelet granules at very high concentration...
  2. Rauova L, Hirsch J, Greene T, Zhai L, Hayes V, Kowalska M, et al. Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia. Blood. 2010;116:5021-31 pubmed publisher
    ..We have shown previously that HIT is associated with antibodies to complexes that form between platelet factor 4 and glycosaminoglycan (GAG) side chains on the surface of platelets...
  3. Keith Ho H, McGrath K, Brodbeck K, Palis J, Schick B. Serglycin proteoglycan synthesis in the murine uterine decidua and early embryo. Biol Reprod. 2001;64:1667-76 pubmed
    ..Serglycin proteoglycan may play an important role in uterine decidual function during early postimplantation development. ..
  4. El Golli N, Issertial O, Rosa J, Briquet Laugier V. Evidence for a granule targeting sequence within platelet factor 4. J Biol Chem. 2005;280:30329-35 pubmed
    ..We have recently analyzed granule targeting of platelet factor 4 (PF4), a secretory alpha-granule chemokine, and demonstrated that PF4 alpha-granule storage relied upon ..
  5. de Jong E, de Haas A, Brouwer N, van Weering H, Hensens M, Bechmann I, et al. Expression of CXCL4 in microglia in vitro and in vivo and its possible signaling through CXCR3. J Neurochem. 2008;105:1726-36 pubmed publisher
    ..spliced variant of CXCR3 expressed on microvascular endothelial cells, named CXCR3b, was shown to bind CXCL4. In the periphery, the cellular expression and functions of CXCL4 are well described but in the brain its ..
  6. Chapman L, Aggrey A, Field D, Srivastava K, Ture S, Yui K, et al. Platelets present antigen in the context of MHC class I. J Immunol. 2012;189:916-23 pubmed publisher
    ..Our study demonstrates a novel Ag presentation role for platelets. ..
  7. Smith J, Wadleigh D, Xia Y, Mar R, Herschman H, Lusis A. Cloning and genomic localization of the murine LPS-induced CXC chemokine (LIX) gene, Scyb5. Immunogenetics. 2002;54:599-603 pubmed
    ..The sequence and mapping data suggest that the human ENA78-PBP-PF4 and GCP2- psi PBP-PF4V1 loci arose from an evolutionarily recent duplication of an ancestral locus related to the murine Lix-Pbp-Pf4 locus. ..
  8. Shi G, Field D, Long X, Mickelsen D, Ko K, Ture S, et al. Platelet factor 4 mediates vascular smooth muscle cell injury responses. Blood. 2013;121:4417-27 pubmed publisher
    ..In this study, we demonstrate that the platelet-derived chemokine platelet factor 4 (PF4/CXCL4) stimulates VSMC injury responses both in vitro and in vivo in a mouse carotid ligation model...
  9. Bdeir K, Gollomp K, Stasiak M, Mei J, Papiewska Pajak I, Zhao G, et al. Platelet-Specific Chemokines Contribute to the Pathogenesis of Acute Lung Injury. Am J Respir Cell Mol Biol. 2017;56:261-270 pubmed publisher
    ..whether the two most abundant platelet chemokines, CXCL7, which induces neutrophil chemotaxis and activation, and CXCL4, which does neither, mediate ALI through complementary pathogenic pathways...
  10. Zhang C, Thornton M, Kowalska M, Sachis B, Feldman M, Poncz M, et al. Localization of distal regulatory domains in the megakaryocyte-specific platelet basic protein/platelet factor 4 gene locus. Blood. 2001;98:610-7 pubmed
    The genes for the related human (h) chemokines, PBP (platelet basic protein) and PF4 (platelet factor 4), are within 5.3 kilobases (kb) of each other and form a megakaryocyte-specific gene locus...
  11. Hayes V, Johnston I, Arepally G, McKenzie S, Cines D, Rauova L, et al. Endothelial antigen assembly leads to thrombotic complications in heparin-induced thrombocytopenia. J Clin Invest. 2017;127:1090-1098 pubmed publisher
    ..thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies against complexes between human platelet factor 4 (hPF4) and heparin...
  12. Kuroishi T, Bando K, Tanaka Y, Shishido K, Kinbara M, Ogawa T, et al. CXCL4 is a novel nickel-binding protein and augments nickel allergy. Clin Exp Allergy. 2017;47:1069-1078 pubmed publisher
    ..Mass spectrometry and Western blotting detected CXCL4 in the active fraction...
  13. Watanabe O, Natori K, Tamari M, Shiomoto Y, Kubo S, Nakamura Y. Significantly elevated expression of PF4 (platelet factor 4) and eotaxin in the NOA mouse, a model for atopic dermatitis. J Hum Genet. 1999;44:173-6 pubmed
    ..Our results suggested that increased expression of PF4 may play an important role in the etiology of allergic dermatitis. ..
  14. Lambert M, Wang Y, Bdeir K, Nguyen Y, Kowalska M, Poncz M. Platelet factor 4 regulates megakaryopoiesis through low-density lipoprotein receptor-related protein 1 (LRP1) on megakaryocytes. Blood. 2009;114:2290-8 pubmed publisher
    b>Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis, but its mechanism of action had not been addressed...
  15. Joglekar M, Khandelwal S, Cines D, Poncz M, Rauova L, Arepally G. Heparin enhances uptake of platelet factor 4/heparin complexes by monocytes and macrophages. J Thromb Haemost. 2015;13:1416-27 pubmed publisher
    ..Taken together, these studies establish a distinct role for heparin in enhancing antigen uptake and activation of the initial steps in the cellular immune response to PF4-containing complexes. ..
  16. Jian J, Pang Y, Yan H, Min Y, Achyut B, Hollander M, et al. Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis. Oncotarget. 2017;8:27725-27739 pubmed publisher
    ..Here we report platelet factor 4 (PF4), or CXCL4, but not the other family members CXCL9, 10, and 11, was produced at higher levels in the ..
  17. Nagata M, Ito T, Arimitsu N, Koyama H, Sekimizu K. Transcription arrest relief by S-II/TFIIS during gene expression in erythroblast differentiation. Genes Cells. 2009;14:371-80 pubmed publisher
    ..These results suggest that S-II is involved in transcription of the Bcl-x and beta(major)-globin gene during erythroblast differentiation, by relieving transcription arrest or affecting histone modification on chromatin template. ..
  18. Muthig V, Gilsbach R, Haubold M, Philipp M, Ivacevic T, Gessler M, et al. Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient mice. Circ Res. 2007;101:682-91 pubmed
  19. Carramolino L, Fuentes J, García Andrés C, Azcoitia V, Riethmacher D, Torres M. Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis. Circ Res. 2010;106:1197-201 pubmed publisher
    ..In addition to their known protective function in the response accidental vascular injury, platelets are also required during embryonic lymphangiogenesis for the separation of the nascent lymphatic vasculature from blood vessels. ..
  20. Sinclair A, Park L, Shah M, Drotar M, Calaminus S, Hopcroft L, et al. CXCR2 and CXCL4 regulate survival and self-renewal of hematopoietic stem/progenitor cells. Blood. 2016;128:371-83 pubmed publisher
    ..In human CD34(+) hematopoietic cells, knockdown of CXCL4 or pharmacologic inhibition of the chemokine receptor CXCR2, significantly decreased cell viability and colony ..
  21. Love M, Millholland M, Mishra S, Kulkarni S, Freeman K, Pan W, et al. Platelet factor 4 activity against P. falciparum and its translation to nonpeptidic mimics as antimalarials. Cell Host Microbe. 2012;12:815-23 pubmed publisher
    ..Therefore, we screened a panel of HDPs and determined that human platelet factor 4 (hPF4) kills malaria parasites inside erythrocytes by selectively lysing the parasite digestive vacuole (DV)...
  22. Nesmelova I, Sham Y, Dudek A, van Eijk L, Wu G, Slungaard A, et al. Platelet factor 4 and interleukin-8 CXC chemokine heterodimer formation modulates function at the quaternary structural level. J Biol Chem. 2005;280:4948-58 pubmed
    ..This concept, in turn, has implications for designing chemokine/cytokine variants with modified biological properties. ..
  23. Briquet Laugier V, Lavenu Bombled C, Schmitt A, Leboeuf M, Uzan G, Dubart Kupperschmitt A, et al. Probing platelet factor 4 alpha-granule targeting. J Thromb Haemost. 2004;2:2231-40 pubmed
    ..We have elected to study the granule storage of platelet factor 4 (PF4), a well-known platelet alpha-granule protein...
  24. Dubrac A, Quemener C, Lacazette E, Lopez F, Zanibellato C, Wu W, et al. Functional divergence between 2 chemokines is conferred by single amino acid change. Blood. 2010;116:4703-11 pubmed publisher
    b>CXCL4 and CXCL4L1 are 2 closely related CXC chemokines that exhibit potent antiangiogenic activity...
  25. Hwaiz R, Rahman M, Zhang E, Thorlacius H. Platelet secretion of CXCL4 is Rac1-dependent and regulates neutrophil infiltration and tissue damage in septic lung damage. Br J Pharmacol. 2015;172:5347-59 pubmed publisher
    ..We hypothesized that platelet-derived CXCL4 might support pulmonary neutrophilia in a murine model of abdominal sepsis...
  26. Mitsui T, Taniguchi N, Kawasaki N, Kagami Y, Arita J. Fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces expression of the chemokine genes Cxcl4 and Cxcl7 in the perinatal mouse brain. J Appl Toxicol. 2011;31:279-84 pubmed publisher
    ..5 was profiled by DNA microarray analysis. The analysis revealed that the expression of two chemokine genes, Cxcl4 and Cxcl7, was up-regulated by TCDD exposure...
  27. Kowalska M, Zhao G, Zhai L, David G, Marcus S, Krishnaswamy S, et al. Modulation of protein C activation by histones, platelet factor 4, and heparinoids: new insights into activated protein C formation. Arterioscler Thromb Vasc Biol. 2014;34:120-6 pubmed publisher
    ..whether histones can modulate aPC generation in a manner similar to another positively charged molecule, platelet factor 4, and how heparinoids (unfractionated heparin or oxygen-desulfated unfractionated heparin with marked ..
  28. Lambert M, Meng R, Xiao L, Harper D, Marks M, Kowalska M, et al. Intramedullary megakaryocytes internalize released platelet factor 4 and store it in alpha granules. J Thromb Haemost. 2015;13:1888-99 pubmed publisher
    Megakaryocytes express and store platelet factor 4 (PF4) in alpha granules. In vivo, PF4 is a clinically relevant, negative regulator of megakaryopoiesis and hematopoietic stem cell replication...
  29. Reilly M, Taylor S, Franklin C, Sachais B, Cines D, Williams K, et al. Prothrombotic factors enhance heparin-induced thrombocytopenia and thrombosis in vivo in a mouse model. J Thromb Haemost. 2006;4:2687-94 pubmed
    ..The development of antibodies that react with complexes of heparin and platelet factor 4 (PF4) is fundamental to the development of the disease...
  30. Bruns I, Lucas D, Pinho S, Ahmed J, Lambert M, Kunisaki Y, et al. Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion. Nat Med. 2014;20:1315-20 pubmed publisher
    ..expression analyses revealed that MKs are the source of chemokine C-X-C motif ligand 4 (CXCL4, also named platelet factor 4 or PF4) in the bone marrow, and we found that CXCL4 regulates HSC cell cycle activity...
  31. Shi G, Field D, Ko K, Ture S, Srivastava K, Levy S, et al. Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection. J Clin Invest. 2014;124:543-52 pubmed publisher
    ..Here we discovered that chemokine platelet factor 4 (PF4) is a negative regulator of Th17 differentiation...
  32. Thomasset N, Lochter A, Sympson C, Lund L, Williams D, Behrendtsen O, et al. Expression of autoactivated stromelysin-1 in mammary glands of transgenic mice leads to a reactive stroma during early development. Am J Pathol. 1998;153:457-67 pubmed
    ..We propose that the highly reactive stroma provides a prelude to breast epithelial tumors observed in these animals. ..
  33. Kitajima K, Kojima M, Kondo S, Takeuchi T. A role of jumonji gene in proliferation but not differentiation of megakaryocyte lineage cells. Exp Hematol. 2001;29:507-14 pubmed
    ..The loss of the jumonji gene causes an increase in the number of megakaryocyte lineage cells. Our data suggest that the jumonji gene regulates proliferation but not differentiation of megakaryocyte lineage cells. ..
  34. Krauel K, Pötschke C, Weber C, Kessler W, Fürll B, Ittermann T, et al. Platelet factor 4 binds to bacteria, [corrected] inducing antibodies cross-reacting with the major antigen in heparin-induced thrombocytopenia. Blood. 2011;117:1370-8 pubmed publisher
    ..heparin-induced thrombocytopenia (HIT), is induced by antibodies specific for complexes of the chemokine platelet factor 4 (PF4) and the polyanion heparin...
  35. Lapchak P, Ioannou A, Rani P, Lieberman L, Yoshiya K, Kannan L, et al. The role of platelet factor 4 in local and remote tissue damage in a mouse model of mesenteric ischemia/reperfusion injury. PLoS ONE. 2012;7:e39934 pubmed publisher
    ..However the contribution of platelets and their products such as Platelet Factor 4 (PF4; CXCL4), during the pathogenesis of IR injury has not been thoroughly investigated...
  36. Reilly M, Taylor S, Hartman N, Arepally G, Sachais B, Cines D, et al. Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcgammaRIIA. Blood. 2001;98:2442-7 pubmed
    ..Interactions between heparin, human platelet factor 4 (hPF4), antibodies to the hPF4/heparin complex, and the platelet Fc receptor (FcR) for immunoglobulin G, ..
  37. Pang L, Xue H, Szalai G, Wang X, Wang Y, Watson D, et al. Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins. Blood. 2006;108:2198-206 pubmed
    ..reduced expression of genes associated with late stages of maturation (glycoprotein [GP] Ibalpha, GPIX, and platelet factor 4 [PF4]), whereas GABPalpha-deficient megakaryocytes were mostly impaired in the expression of early ..
  38. Tutwiler V, Madeeva D, Ahn H, Andrianova I, Hayes V, Zheng X, et al. Platelet transactivation by monocytes promotes thrombosis in heparin-induced thrombocytopenia. Blood. 2016;127:464-72 pubmed publisher
    ..We have shown that monocytes complexed with surface-bound platelet factor 4 (PF4) activated by HIT antibodies contribute to the prothrombotic state in vivo, but the mechanism by which ..
  39. Suvarna S, Espinasse B, Qi R, Lubica R, Poncz M, Cines D, et al. Determinants of PF4/heparin immunogenicity. Blood. 2007;110:4253-60 pubmed
  40. Ghanem L, Kromer A, Silverman I, Chatterji P, Traxler E, Penzo Méndez A, et al. The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development. Mol Cell Biol. 2016;36:304-19 pubmed publisher
    ..These data further provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved an essential function(s) in the mammalian genome. ..
  41. Srivastava K, Field D, Aggrey A, Yamakuchi M, Morrell C. Platelet factor 4 regulation of monocyte KLF4 in experimental cerebral malaria. PLoS ONE. 2010;5:e10413 pubmed publisher
    ..One of the platelet derived mediators we have identified as particularly important is platelet factor 4/CXCL4...
  42. Wetterholm E, Linders J, Merza M, Regner S, Thorlacius H. Platelet-derived CXCL4 regulates neutrophil infiltration and tissue damage in severe acute pancreatitis. Transl Res. 2016;176:105-18 pubmed publisher
    ..Platelets contain a wide spectrum of different pro-inflammatory compounds, such as chemokines. CXCL4 (platelet factor 4) is one of the most abundant chemokine in platelets, and we hypothesized that CXCL4 might be involved in ..
  43. Mueller A, Meiser A, McDonagh E, Fox J, Petit S, Xanthou G, et al. CXCL4-induced migration of activated T lymphocytes is mediated by the chemokine receptor CXCR3. J Leukoc Biol. 2008;83:875-82 pubmed publisher
    The chemokine CXCL4/platelet factor-4 is released by activated platelets in micromolar concentrations and is a chemoattractant for leukocytes via an unidentified receptor...
  44. Wang H, Zhang W, Tang R, Hebbel R, Kowalska M, Zhang C, et al. Core2 1-6-N-glucosaminyltransferase-I deficiency protects injured arteries from neointima formation in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 2009;29:1053-9 pubmed publisher
    ..Endothelial regeneration was associated with reduced accumulation of platelet factor 4 (PF4) at injured sites...
  45. Cervi D, Pak B, Venier N, Sugar L, Nam R, Fleshner N, et al. Micronutrients attenuate progression of prostate cancer by elevating the endogenous inhibitor of angiogenesis, platelet factor-4. BMC Cancer. 2010;10:258 pubmed publisher
  46. Redmond L, Dumur C, Archer K, Haar J, Lloyd J. Identification of erythroid-enriched gene expression in the mouse embryonic yolk sac using microdissected cells. Dev Dyn. 2008;237:436-46 pubmed publisher
    ..Quantitative real-time polymerase chain reaction was used to verify that platelet factor 4, reelin, thrombospondin-1, and muscleblind-like 1 mRNA is erythroid-enriched...
  47. Kowalska M, Krishnaswamy S, Rauova L, Zhai L, Hayes V, Amirikian K, et al. Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HIT. Blood. 2011;118:2882-8 pubmed publisher
    Heparin-induced thrombocytopenia (HIT) is caused by antibodies that recognize complexes between platelet factor 4 (PF4) and heparin or glycosaminoglycan side chains...
  48. Zaldivar M, Pauels K, von Hundelshausen P, Berres M, Schmitz P, Bornemann J, et al. CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis. Hepatology. 2010;51:1345-53 pubmed publisher
    ..Here, we investigate the platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) as a molecular mediator of fibrotic liver damage...
  49. Iida Y, Xu B, Xuan H, Glover K, Tanaka H, Hu X, et al. Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression. Arterioscler Thromb Vasc Biol. 2013;33:718-26 pubmed publisher
    ..We examined the ability of MKEY, a peptide inhibitor of CXCL4-CCL5 interaction, to influence AAA progression in murine models...