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診断マーカー開発

がんの判定、及び生活習慣病がもたらす疾病リスクを予測するための、診断薬を開発する事業です。
がん細胞や疾患に係わる細胞が血液中に放出する特異的な微量なタンパク質濃度を測定し、特定の疾病にかかっている可能性を判定します。

血管炎症マーカー Pentraxin3 ( PTX3 / TSG-14 )

2008年9月26日

Pentraxin3 (ペントラキシン3 PTX3/TSG-14)は、直接そして短時間に、血管の炎症を反映するマーカーとして、期待されています。 

ペルセウスプロテオミクスでは、この炎症マーカーであるPTX3を高感度/高性度に検出するELISA系の開発(*1)し、現在、このELISA系を用いて、世界中で、臨床的有用性を示すことに成功しています。

キット「Human Pentraxin3 / TSG-14 ELISA System」について

Pentraxin 3 (PTX3/TSG-14) とは

動脈硬化、プラーク形成・進行と破綻の過程に、多くの炎症メディエーターが関与しています(*2)。その中でもよく研究されている炎症タンパク質がC-reactive protein (CRP)で、炎症マーカーとして広く利用されています。

このCRPやSAP(Serum amyloid P component)は、Pentraxin FamilyのShort Pentraxinに分類され、肝臓で合成されることがわかっています (*3-4) 。

Pentraxin3(PTX3)は、Pentraxin familyのLong Pentraxinに分類され、IL-1やTNFの刺激で、動脈硬化と密接な関連をもつ血管内皮細胞や血管平滑筋マクロファージや、白血球などから直接産生されます(*5-10)。

ヒト臍帯内皮細胞にスタチンを作用させることで、最も発現抑制される遺伝子がPTX3であること(*11)、そして、心筋梗塞患者では早期にPTX3値が上昇すること(*12)なども報告されています。

お問い合わせ先
株式会社ペルセウスプロテオミクス 事業推進部
TEL: 03-5738-1705 / FAX:03-3482-5760
MAIL:ptx3@ppmx.com
PTX3とCRPおよびSAPのアミノ酸配列の違い
PTX3とCRPおよびSAPのアミノ酸配列の違い

PTX3の免疫応答
PTX3の免疫応答

PTX3の産生場所
PTX3の産生場所

Human Pentraxin 3 / TSG-14 ELISA Systemを用いた論文

1  Arterioscler Thromb Vasc Biol. 2007 ; 27(1) : 161-7.
Establishment of a High Sensitivity Plasma Assay for Human Pentraxin3 as a Marker for Unstable Angina Pectoris
Inoue K, Sugiyama A, Reid PC, Ito Y, Miyauchi K, Mukai S, Sagara M, Miyamoto K, Satoh H, Kohno I, Kurata T, Ota H, Mantovani A, Hamakubo T, Daida H, and Kodama T.

2 Clin J Am Soc Nephrol. 2007 ; 2(5) : 889-97.
Plasma pentraxin 3 in patients with chronic kidney disease: associations with renal function, protein-energy wasting, cardiovascular disease, and mortality.
Tong M, Carrero JJ, Qureshi AR, Anderstam B, Heimburger O, Barany P, Axelsson J, Alvestrand A, Stenvinkel P, Lindholm B, Suliman ME.

3 Cell Immunol. 2007 ; 248(2) : 86-94.
Lipopolysaccharide induced expression of pentraxin 3 in human neutrophils and monocyte-derived macrophages.
Imamura M, Kawasaki T, Savchenko AS, Ohashi R, Jiang S, Miyamoto K, Ito Y, Iwanari H, Sagara M, Tanaka T, Hamakubo T, Kodama T, Uchiyama M, Naito M.

4 J Pathol. 2008 ; 215(1) : 48-55.
Expression of pentraxin 3 (PTX3) in human atherosclerotic lesions.
Savchenko A, Imamura M, Ohashi R, Jiang S, Kawasaki T, Hasegawa G, Emura I, Iwanari H, Sagara M, Tanaka T, Hamakubo T, Kodama T, Naito M.

5 Atherosclerosis 2008 ; 197(1) : 368-74.
Pentraxin3 is a novel marker for stent-induced inflammation and neointimal thickening
Kotooka N, Inoue T, Fujimatsu D, Morooka T, Hashimoto S, Hikichi Y, Uchida T, Sugiyama A, Node K.

6 Am Heart J. 2008 ; 155(1) : 75-81.
Pentraxin 3, a new marker for vascular inflammation, predicts adverse clinical outcomes in patients with heart failure.
Suzuki S, Takeishi Y, Niizeki T, Koyama Y, Kitahara T, Sasaki T, Sagara M, Kubota I.

7 Dig Dis Sci. 2008 ; 53(7) : 1910-6.
Increased Expression of Long Pentraxin PTX3 in Inflammatory Bowel Diseases.
Kato S, Ochiai M, Sakurada T, Ohno S, Miyamoto K, Sagara M, Ito M, Takeuchi K, Imaki J, Itoh K, Yakabi K.

8 Int J Cardiol. 2008 ; 130(1) : 19-22.
Prognostic value of pentraxin 3 in patients with chronic heart failure.
Kotooka N, Inoue T, Aoki S, Anan M, Komoda H, Node K.

9 Clin Chem Lab Med. 2009 ; 47(4) : 471-7.
Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy poulations.
Yamasaki K, Kurimura M, Kasai T, Sagara M, Kodama T, Inoue K.

10 Journal of Analytical Bio-Science 2010 ; 33(4) : 289-97
Pentraxin 3
Inoue K.

11 Journal of Analytical Bio-Science 2010 ; 33(4) : 298-306
The role of PTX3 in emergency and critical care
Yamaguchi N.

12 Journal of Analytical Bio-Science 2010 ; 33(4) : 307-12
Pentraxin 3 as a cardiovascular biomarker
Kotooka N.

13 Journal of Analytical Bio-Science 2010 ; 33(4) : 313-20
The role of PTX3 in the pentraxin family
Maemura K, Shiga T.

14 Journal of Analytical Bio-Science 2010 ; 33(4) : 321-8
Clinical meaning value of long pentraxin PTX3 for patients with inflammatory bowel disease
Kato S, Yakabi K.

15 Journal of Analytical Bio-Science 2010 ; 33(4) : 329-38
Neutrophils and pentraxin 3
Naito M, Savchenko S. A, Inoue A.

16 Journal of Analytical Bio-Science 2010 ; 33(4) : 339-46
Metabolic syndrome and pentraxin 3
Ogawa T, Imamura T, Kitamura K.

17 Journal of Analytical Bio-Science 2010 ; 33(4) : 347-54
Coronary plaque, thrombosis and PTX3
Hatakeyama K, Asada Y.

Reference

*1 Arteriosclerosis, Thrombosis, and Vascular Biology 2006
Establishment of a High Sensitivity Plasma Assay for Human Pentraxin3 as a Marker for Unstable Angina Pectoris
Inoue K.et al .

*2. Nature. 2000 Sep 14;407(6801):233-41. PMID: 11001066
Atherosclerosis.
Lusis AJ. et al.

*3. Immunol Today. 1994 Feb;15(2):74-80. PMID: 7512342
The acute phase response.
Baumann H. et al.

*4. Immunol Today. 1994 Feb;15(2):81-8. PMID: 8155266
The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein
Steel DM. et al.

*5. J Immunol. 1994 Oct 15;153(8):3700-7. PMID: 7523502
Relationship of TSG-14 protein to the pentraxin family of major acute phase proteins.
Lee GW. et al.

*6. J Biol Chem. 1997 Dec 26;272(52):32817-23. PMID: 9407058
Multimer formation and ligand recognition by the long pentraxin PTX3.
Bottazzi B. et al.

*7. Blood. 1996 Mar 1;87(5):1862-72. PMID: 8634434
Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites.
Introna M. et al.

*8. Annu Rev Immunol. 2005;23:337-66. Review. PMID: 15771574
Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility.
Garlanda C. et al.

*9. J Biol Chem. 1997 Mar 28;272(13):8172-8. PMID: 9079634
Characterization of the promoter for the human long pentraxin PTX3. Role of NF-kappaB in tumor necrosis factor-alpha and interleukin-1beta regulation.
Basile A, et al.

*10. J Exp Med. 2007;204(4):793-804.
The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps.
Jaillon, S. et al.

*11. J Atheroscler Thromb. 2002;9(4):178-83. PMID: 12226549
The effect of statins on mRNA levels of genes related to inflammation, coagulation, and vascular constriction in HUVEC. Human umbilical vein endothelial cells.
Morikawa S, et al.

*12. Circulation. 2000 Aug 8;102(6):636-41. PMID: 10931803
PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans.
Peri G. et al.

その他のReference

1. Blood. 1994;84(10):3483-93.
Inducible expression of PTX3, a new member of the pentraxin family, in human mononuclear phagocytes.
Alles, VV. et al.

2. Cytokine Growth Factor Rev. 2004;15(2-3):129-46.
Cytokine-induced gene expression at the crossroads of innate immunity, inflammation and fertility: TSG-6 and PTX3/TSG-14.
Wisniewski, HG. and Vilcek, J.

3. J Leukoc Biol. 2006;79(5):909-12.
The long pentraxin PTX3 as a link among innate immunity, inflammation, and female fertility.
Bottazzi, B. et al.

4. J. Neuroimmunol. 2000;106(1-2):87-94.
Inducible expression of the long pentraxin PTX3 in the central nervous system.
Polentarutti, N et al.

5. Development. 2004;131(7):1577-86.
PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in vivo fertilization.
Salustri, A. et al.

6. Arterioscler Thromb Vasc Biol. 2005;25(9):1837-42.
Pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo.
Camozzi, M. et al.

7. Immunity. 2005;22(5):551-60.
Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors.
Jeannin, P. et al.

8. J Biol Chem. 1992;267(31):22190-7.
Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component.
Breviario, F. et al.

9. Infect Immun. 1997;65(4):1345-50.
Expression of a long pentraxin, PTX3, by monocytes exposed to the mycobacterial cell wall component lipoarabinomannan.
Vouret-Craviari, V. et al.

10. Blood. 2000;96(13):4300-6.
The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells.
Rovere, P. et al.

11. Nature. 2002;420(6912):182-6.
Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response.
Garlanda, C. et al.

12. Eur J Immunol. 2003;33(2):465-73.
Biochemical and functional characterization of the interaction between pentraxin 3 and C1q.
Nauta, AJ. et al.

13. J Leukoc Biol. 2004;75(4):649-56.
PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages.
Diniz, SN. et al.

14. J Immunol. 2005;175(12):8303-11.
TNFalpha-induced long pentraxin PTX3 expression in human lung epithelial cells via JNK.
Han, B. et al.

15. Blood. 2006;107(1):151-8.
The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens.
Baruah, P. et al.

16. J Leukoc Biol. 2006;79(4):797-802.
Regulation of PTX3, a key component of humoral innate immunity in human dendritic cells: stimulation by IL-10 and inhibition by IFN-gamma.
Doni, A. et al.

17. Cell Immunol. 2007;248(2):86-94.
Lipopolysaccharide induced expression of pentraxin 3 in human neutrophils and monocyte-derived macrophages.
Imamura, M. et al.

18. Dig Dis Sci. 2008;53(7):1910-6.
Increased expression of long pentraxin PTX3 in inflammatory bowel diseases.
Kato, S. et al.

19. J Pathol. 2008;215(1):48-55.
Expression of pentraxin 3 (PTX3) in human atherosclerotic lesions.
Savchenko, A. et al.

20. Arthritis Rheum. 2001;44(12):2841-50.
PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation.
Fazzini, F. et al.

21. Circulation. 2004;110(16):2349-54.
Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction.
Latini R. et al.

22. Clin J Am Soc Nephrol. 2007;2(5):889-97.
Plasma pentraxin 3 in patients with chronic kidney disease: associations with renal function, protein-energy wasting, cardiovascular disease, and mortality.
Tong, M. et al.

23. Atherosclerosis. 2008;197(1):368-74.
Pentraxin3 is a novel marker for stent-induced inflammation and neointimal thickening.
Kotooka, N. et al.

24. Int J Cardiol. 2008;130(1):19-22.
Prognostic value of pentraxin 3 in patients with chronic heart failure.
Kotooka, N. et al.

25. Clin J Am Soc Nephrol. 2008;3(4):976-85.
Novel links between the long pentraxin 3, endothelial dysfunction, and albuminuria in early and advanced chronic kidney disease.
Suliman, ME. et al.

26. Clin Chem Lab Med. 2009;47(4):471-7.
Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy populations.
Yamasaki K, et al.
    
   
【関連項目】
Human Pentraxin3/TSG-14 ELISA Systemについて
Human Pentraxin3/TSG14 ELISA System カタログ
Human Pentraxin3/TSG14 ELISA System 製品Instruction