血小板第4因子

関: platelet factor 4

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the 16th letter of the Roman alphabet (同)p

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/04/30 00:15:23」(JST)

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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 III 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 CXCR3B.^[4]

Clinical significance

The heparin:PF4 complex is the antigen in heparin-induced thrombocytopenia, 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]

The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.^[7]

References

^ ^a ^b 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. PMID 1695112.
^ O'Donovan N, Galvin M, Morgan J (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenet Cell Genet 84 (1–2): 39–42. doi:10.1159/000015209. PMID 10343098.
^ "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)".
^ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (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". J Exp Med 197 (11): 1537–1549. doi:10.1084/jem.20021897. PMC 2193908. PMID 12782716.
^ Warkentin TE (March 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". N. Engl. J. Med. 356 (9): 891–893. doi:10.1056/NEJMp068309. PMID 17329695.
^ Warkentin TE, Makris M, Jay RM, Kelton JG (July 2008). "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". Am. J. Med. 121 (7): 632–636. doi:10.1016/j.amjmed.2008.03.012. PMID 18589060.
^ Love MS, Millholland MG, Mishra S, Kulkarni S, Freeman KB, Pan W, Kavash RW, Costanzo MJ, Jo H, Daly TM, Williams DR, Kowalska MA, Bergman LW, Poncz M, Degrado WF, Sinnis P, Scott RW, Greenbaum DC (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. PMID 23245326.

External links

Platelet factor 4 at the US National Library of Medicine Medical Subject Headings (MeSH)

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

UpToDate Contents

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1. ヘパリン起因性血小板減少症の臨床症状および診断 clinical presentation and diagnosis of heparin induced thrombocytopenia
2. ヘパリン起因性血小板減少症のマネージメント management of heparin induced thrombocytopenia
3. Approach to the patient with a leg ulcer
4. 血小板機能検査 platelet function testing
5. 薬剤性血小板減少症 drug induced thrombocytopenia

English Journal

Host response: PF4 - platelets' poison.

David R.
Nature reviews. Microbiology.Nat Rev Microbiol.2013 Jan 3. doi: 10.1038/nrmicro2955. [Epub ahead of print]
PMID 23268231

Evaluation of Circuit and AV Fistula Clotting and Detection of Anti-PF4/Heparin Complex Antibodies in Hemodialysis Patients Suspected of Having Heparin-Induced Thrombocytopenia.

Matsuo T, Wanaka K, Walenga JM.Source1Hyogo Prefectural Awaji Hospital, Sumoto, Hyogo, Japan.
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.Clin Appl Thromb Hemost.2013 Jan;19(1):73-8. doi: 10.1177/1076029612436676. Epub 2012 Feb 16.
A retrospective study was performed to elucidate the characteristics of heparin-induced thrombocytopenia (HIT) in newly treated hemodialysis (HD) patients who essentially required anticoagulation with unfractionated heparin (UFH). Seventy-eight patients suspected of having HIT within 3 months of sta
PMID 22345486

Platelet IκB Kinase-β Deficiency Increases Mouse Arterial Neointima Formation via Delayed Glycoprotein Ibα Shedding.

Wei S, Wang H, Zhang G, Lu Y, An X, Ren S, Wang Y, Chen Y, White JG, Zhang C, Simon DI, Wu C, Li Z, Huo Y.SourceThe Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Emergency, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Arteriosclerosis, thrombosis, and vascular biology.Arterioscler Thromb Vasc Biol.2012 Dec 13. [Epub ahead of print]
OBJECTIVE: On the luminal surface of injured arteries, platelet activation and leukocyte-platelet interactions are critical for the initiation and progression of arterial restenosis. The transcription factor nuclear factor-κB is a critical molecule in platelet activation. Here, we investigated the
PMID 23241410

Japanese Journal

ヘパリン起因性血小板減少症の診断における抗血小板第4因子/ヘパリン複合体抗体測定の意義

松尾武文
臨床検査 58(4), 518-522, 2014-04
NAID 40020040806

Neutrophil Phagocytosis of Platelets in the Early Phase of 2,4,6-trinitro-1-chlorobenzene (TNCB)-induced Dermatitis in Mice

Daito Junko,Harada Yoshinori,Dai Ping,Yamaoka Yoshihisa,Tamagawa-Mineoka Risa,Katoh Norito,Takamatsu Tetsuro
ACTA HISTOCHEMICA ET CYTOCHEMICA, 2014
… Four hours after elicitation, aggregates of CD41-positive platelets were adhered to CD31-positive endothelial cells within the vessels, and CD62P and PF4, markers of activated platelets, were expressed on platelet aggregates. … Twenty-four hours after elicitation, the number of Ly-6G-positive neutrophils ingesting fragmented CD41-positive platelets outside vessels was increased, and CD62P and PF4 expression on the phagocytosed platelets was no longer observed. …
NAID 130003390849

第46回北海道支部総会シンポジウム : 血小板第4因子/ ヘパリン複合体抗体測定の新しい流れ

阪田敏幸
臨床病理 : 日本臨床検査医学会誌 61(2), 137-143, 2013-02
NAID 40019618200

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リンク元	「血小板第4因子」
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「血小板第4因子」

Platelet factor 4
	; PDB rendering based on 1f9q.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1DN3, 1F9Q, 1F9R, 1F9S, 1PFM, 1PFN, 1RHP
Identifiers
Symbols	PF4 ; CXCL4; PF-4; SCYB4
External IDs	OMIM: 173460 MGI: 1888711 HomoloGene: 87791 GeneCards: PF4 Gene
Gene ontology
Molecular function	• chemokine activity; • heparin binding;
Cellular component	• extracellular region; • extracellular space; • platelet alpha granule lumen;
Biological process	• platelet degranulation; • immune response; • blood coagulation; • positive regulation of gene expression; • positive regulation of macrophage derived foam cell differentiation; • negative regulation of angiogenesis; • cytokine-mediated signaling pathway; • platelet activation; • leukocyte chemotaxis; • positive regulation of tumor necrosis factor production; • negative regulation of apoptotic process; • negative regulation of MHC class II biosynthetic process; • positive regulation of macrophage differentiation; • negative regulation of megakaryocyte differentiation; • negative regulation of cytolysis;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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英: platelet factor 4, PF4
関: 血小板

-PF4

「P」

　　[★]

「PF」

　　[★] 平行線維 parallel fiber parallel fibre

[Eisman_1990-1] 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. PMID 1695112.

[2] O'Donovan N, Galvin M, Morgan J (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenet Cell Genet 84 (1–2): 39–42. doi:10.1159/000015209. PMID 10343098.

[3] "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)".

[4] Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (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". J Exp Med 197 (11): 1537–1549. doi:10.1084/jem.20021897. PMC 2193908. PMID 12782716.

[5] Warkentin TE (March 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". N. Engl. J. Med. 356 (9): 891–893. doi:10.1056/NEJMp068309. PMID 17329695.

[6] Warkentin TE, Makris M, Jay RM, Kelton JG (July 2008). "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". Am. J. Med. 121 (7): 632–636. doi:10.1016/j.amjmed.2008.03.012. PMID 18589060.

[pmid23245326-7] Love MS, Millholland MG, Mishra S, Kulkarni S, Freeman KB, Pan W, Kavash RW, Costanzo MJ, Jo H, Daly TM, Williams DR, Kowalska MA, Bergman LW, Poncz M, Degrado WF, Sinnis P, Scott RW, Greenbaum DC (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. PMID 23245326.

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PF4