肝疾患とキマーゼ
ヒト循環血中でのアンジオテンシンI(AI)からアンジオテンシンII(AII)への変換は, その大部分がアンジオテンシン変換酵素(ACE)に依存している. ところが, ACEによらないA II産生経路があり, それにセリンプロテアーゼが関与することが証明されている1. セリンプロテアーゼの一つであるキマーゼは, 主に肥満細胞の分泌顆粒に存在して非ACE経路のAII産生に働いている2, 3. 近年, 肥満細胞と線維芽細胞との関連が注目され, キマーゼを分泌する肥満細胞が線維芽細胞のもとに間質結合織内で分化し, 心筋, 腎などにおける線維化に関与していることが明らかになった4-7. 一方, AIIの...
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| Published in | 日本医科大学医学会雑誌 Vol. 1; no. 4; pp. 168 - 174 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本医科大学医学会
2005
|
| Online Access | Get full text |
| ISSN | 1349-8975 1880-2877 |
| DOI | 10.1272/manms.1.168 |
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| Abstract | ヒト循環血中でのアンジオテンシンI(AI)からアンジオテンシンII(AII)への変換は, その大部分がアンジオテンシン変換酵素(ACE)に依存している. ところが, ACEによらないA II産生経路があり, それにセリンプロテアーゼが関与することが証明されている1. セリンプロテアーゼの一つであるキマーゼは, 主に肥満細胞の分泌顆粒に存在して非ACE経路のAII産生に働いている2, 3. 近年, 肥満細胞と線維芽細胞との関連が注目され, キマーゼを分泌する肥満細胞が線維芽細胞のもとに間質結合織内で分化し, 心筋, 腎などにおける線維化に関与していることが明らかになった4-7. 一方, AIIの働きの一つに各種臓器における細胞増殖, 細胞外基質産生を促進する作用があることが明らかにされている8, 9. そこでわれわれは, 肥満細胞の特異的な酵素であるキマーゼの測定方法を確立しキマーゼが肝線維形成に関与しているかどうかを調べるため, 血清ならびに肝組織中の活性測定を試みた. |
|---|---|
| AbstractList | ヒト循環血中でのアンジオテンシンI(AI)からアンジオテンシンII(AII)への変換は, その大部分がアンジオテンシン変換酵素(ACE)に依存している. ところが, ACEによらないA II産生経路があり, それにセリンプロテアーゼが関与することが証明されている1. セリンプロテアーゼの一つであるキマーゼは, 主に肥満細胞の分泌顆粒に存在して非ACE経路のAII産生に働いている2, 3. 近年, 肥満細胞と線維芽細胞との関連が注目され, キマーゼを分泌する肥満細胞が線維芽細胞のもとに間質結合織内で分化し, 心筋, 腎などにおける線維化に関与していることが明らかになった4-7. 一方, AIIの働きの一つに各種臓器における細胞増殖, 細胞外基質産生を促進する作用があることが明らかにされている8, 9. そこでわれわれは, 肥満細胞の特異的な酵素であるキマーゼの測定方法を確立しキマーゼが肝線維形成に関与しているかどうかを調べるため, 血清ならびに肝組織中の活性測定を試みた. |
| Author | 里村, 克章 清水, 秀治 古明地, 弘和 大本, 安一 勝田, 悌実 |
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| References | 8. Algermissen B, Hermes B, Feldmann-Boeddeker I, Bauer F, Henz BM: Mast cell chymase and tryptase during tissue turnover: analysis on in vitromitogenesis of fibroblast and alterations in cutaneus scars. Exp Dermatol 1999; 8: 193-198. 1. Reilly CF, Tewksbury DA, Schechter NM, Travis J: Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases. J Biol Chem 1982; 257: 8619-8622. 21. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, Tsujinoue H, Hukui H: Angiotensin-II type 1 recepter interaction is a major regulator for liver fibrosis development in rats. Hepatology 2001; 34: 745-750. 4. Marone G, de Crescnzo G, Florio G, Granata F, Dente V, Genovese A: Immunological modulation of human cardiac mast cell. Neurochem Res 1999; 91: 1195-1202. 12. Shimizu S, Satomura K, Aramaki T, Katsuta Y, Takano T, Omoto T: Hepatic chymase level in chronic hepatitis: co-localization of chymase with fibrosis. Hepatol Res 2003; 27: 57-61. 11. Urata H, Kinoshita A, Misono KS, Bumpus FM, Husain A: Identification of a highly specific chymase as the major angiotensinII-forming enzyme in the human heart. J Biol Chem 1990; 265: 22348-22357. 20. Wei HS, Lu HM, Li DG, Zhan YT, Wang ZR, Huang X, Cheng JL, Xu QF: The regulatory role of AT I receptor on activated HSCs in hepatic fibrogenesis: effects of RAS inhibitors on hepatic fibrosis induced by CCL4. World Gastroentero 2000; 6: 824-828. 5. Shiota N, Jin D, Takai S, Kawamura T, Koyama M, Nakamura N, Miyazaki M: chymase is Activated in the hamster heart following ventricular fibrosis during the chronic Stage of hypertension. FEBS Lett 1997; 406: 301-304. 2. Urata H, Boehn KD, Phillip A, Kinoshita A, Gabrovsek J, Bumpus FM, Husain A: Cellular localization and regional distribution of an angiotensinII-forming Chymase in the heart. J Clin Invest 1993; 91: 1269-1281. 15. Tani K, Ogushi F, Kido H, Kawano T, Kunori Y, Kamimura T, Cui P, Sone S: Chymase is a potent chemoatttactant for human monocytes and neutrophils. J Leukoc Biol 2000; 67: 585-589. 6. Toh T, Toh-Jakatics R, Jim S, Ihara M, Urata H, Takebayashi S: Mast cell rapidly progressive glomerulonephritis. J AM Soc Nephrol 1999; 10: 1498-1505. 10. Satomura K, Shimizu S, Nagato T, Komeichi H, Osuga M, Katsuta Y, Aramaki T, Omoto Y: Establishment of an assay method for human mast cell chymase. Hepatol Res 2002; 24: 361-367. 7. Yamada M, Ueda M, Naruko T, Tanabe S, Young-Sin H, Ikura Y, Ogami M, Takai S, Miyazaki M: mast cell chymase expression and mast cell phenotypes in human rejected kidneys. Kidney Int 2001; 59: 1374-1381. 17. Parits G, Cooper ME, Schembri JM, Tikellis C, Burrel LM, Angus PW: Up-regulation of components of the rennin-angiotensin syatem in the bile duct-ligated rat liver. Gastroenterology 2002; 123: 1667-1676. 16. Baaller R, Sancho-Brau P, Gines P, Lora JM, Al-Garawi A, Sole M, Colmenero J, Nicolas JM, Jimenz W, Weich N, Gutierrez-Ramos J-C, Arroyo V, Rodes J: Activated hepatic stellate cells express the rennin-angiotensin system and synthesize angiotensinII. Gastroenterology 2003; 125: 117-125. 22. Tuncer I, Ozbek H, Ugras S, Bayram I: Anti-fibrogenetic effects of captoril and candesartan cilexetil on the hepatic fibrosis development in rat. Exp Toxic Pathol 2003; 55: 159-166. 3. Nurakami M, Matsuda H, Kubota E, Wakino S, Honda M, Hayashi K, Saruta T: Role of angiotensinII generated by angiotensin converting enzyme-independent pathways in canine kidney. Kidney Int (Suppl) 1997; 52: S132-135. 18. Jonsson JR, Clouston AD, Ando Y, Keleman LI, Horn MJ, Adamson MD, Purdie DM, Powell EE: Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology 2001; 121: 148-155. 14. Satomura K, Yin M, Shimizu S, Kato Y, Nagato T, Komeichi H, Ohsuga M, Katsuta Y, Aramaki T, Omoto Y: Increased chymase in livers with autoimmune disease: Co-localization with fibrosis. J Nippon Med Sch 2003; 70: 490-495. 9. Kofford MW, Schwarz LB, Schechter NM, Yager DR, Diegelmann RF, Graham MF: Cleavage of type I procollagen by human mast cell chymase initiates collagen fibril formation and generates a unique carboxyl-terminal propeptide. J Biol Chem 1997; 272: 7127-7131. 19. Ramalho LN, Ramalho FS, Zucoloto S, Castro-e-Silva Junior O, Correa FM, Elias Junior J, Magalhaes JF: Effect of losartan, an angiotensinIIantagonist, on secondary biliary cirrhosis. Hepato-gastroenterology 2002; 49: 1499-1502. 13. Desmet VJ, Gerber M, Hoofnargle JH, Manns M, Scheuer PJ: Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994; 19: 1513-1520. |
| References_xml | – reference: 13. Desmet VJ, Gerber M, Hoofnargle JH, Manns M, Scheuer PJ: Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994; 19: 1513-1520. – reference: 10. Satomura K, Shimizu S, Nagato T, Komeichi H, Osuga M, Katsuta Y, Aramaki T, Omoto Y: Establishment of an assay method for human mast cell chymase. Hepatol Res 2002; 24: 361-367. – reference: 17. Parits G, Cooper ME, Schembri JM, Tikellis C, Burrel LM, Angus PW: Up-regulation of components of the rennin-angiotensin syatem in the bile duct-ligated rat liver. Gastroenterology 2002; 123: 1667-1676. – reference: 15. Tani K, Ogushi F, Kido H, Kawano T, Kunori Y, Kamimura T, Cui P, Sone S: Chymase is a potent chemoatttactant for human monocytes and neutrophils. J Leukoc Biol 2000; 67: 585-589. – reference: 20. Wei HS, Lu HM, Li DG, Zhan YT, Wang ZR, Huang X, Cheng JL, Xu QF: The regulatory role of AT I receptor on activated HSCs in hepatic fibrogenesis: effects of RAS inhibitors on hepatic fibrosis induced by CCL4. World Gastroentero 2000; 6: 824-828. – reference: 5. Shiota N, Jin D, Takai S, Kawamura T, Koyama M, Nakamura N, Miyazaki M: chymase is Activated in the hamster heart following ventricular fibrosis during the chronic Stage of hypertension. FEBS Lett 1997; 406: 301-304. – reference: 12. Shimizu S, Satomura K, Aramaki T, Katsuta Y, Takano T, Omoto T: Hepatic chymase level in chronic hepatitis: co-localization of chymase with fibrosis. Hepatol Res 2003; 27: 57-61. – reference: 4. Marone G, de Crescnzo G, Florio G, Granata F, Dente V, Genovese A: Immunological modulation of human cardiac mast cell. Neurochem Res 1999; 91: 1195-1202. – reference: 22. Tuncer I, Ozbek H, Ugras S, Bayram I: Anti-fibrogenetic effects of captoril and candesartan cilexetil on the hepatic fibrosis development in rat. Exp Toxic Pathol 2003; 55: 159-166. – reference: 7. Yamada M, Ueda M, Naruko T, Tanabe S, Young-Sin H, Ikura Y, Ogami M, Takai S, Miyazaki M: mast cell chymase expression and mast cell phenotypes in human rejected kidneys. Kidney Int 2001; 59: 1374-1381. – reference: 3. Nurakami M, Matsuda H, Kubota E, Wakino S, Honda M, Hayashi K, Saruta T: Role of angiotensinII generated by angiotensin converting enzyme-independent pathways in canine kidney. Kidney Int (Suppl) 1997; 52: S132-135. – reference: 1. Reilly CF, Tewksbury DA, Schechter NM, Travis J: Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases. J Biol Chem 1982; 257: 8619-8622. – reference: 19. Ramalho LN, Ramalho FS, Zucoloto S, Castro-e-Silva Junior O, Correa FM, Elias Junior J, Magalhaes JF: Effect of losartan, an angiotensinIIantagonist, on secondary biliary cirrhosis. Hepato-gastroenterology 2002; 49: 1499-1502. – reference: 14. Satomura K, Yin M, Shimizu S, Kato Y, Nagato T, Komeichi H, Ohsuga M, Katsuta Y, Aramaki T, Omoto Y: Increased chymase in livers with autoimmune disease: Co-localization with fibrosis. J Nippon Med Sch 2003; 70: 490-495. – reference: 18. Jonsson JR, Clouston AD, Ando Y, Keleman LI, Horn MJ, Adamson MD, Purdie DM, Powell EE: Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology 2001; 121: 148-155. – reference: 16. Baaller R, Sancho-Brau P, Gines P, Lora JM, Al-Garawi A, Sole M, Colmenero J, Nicolas JM, Jimenz W, Weich N, Gutierrez-Ramos J-C, Arroyo V, Rodes J: Activated hepatic stellate cells express the rennin-angiotensin system and synthesize angiotensinII. Gastroenterology 2003; 125: 117-125. – reference: 11. Urata H, Kinoshita A, Misono KS, Bumpus FM, Husain A: Identification of a highly specific chymase as the major angiotensinII-forming enzyme in the human heart. J Biol Chem 1990; 265: 22348-22357. – reference: 2. Urata H, Boehn KD, Phillip A, Kinoshita A, Gabrovsek J, Bumpus FM, Husain A: Cellular localization and regional distribution of an angiotensinII-forming Chymase in the heart. J Clin Invest 1993; 91: 1269-1281. – reference: 6. Toh T, Toh-Jakatics R, Jim S, Ihara M, Urata H, Takebayashi S: Mast cell rapidly progressive glomerulonephritis. J AM Soc Nephrol 1999; 10: 1498-1505. – reference: 9. Kofford MW, Schwarz LB, Schechter NM, Yager DR, Diegelmann RF, Graham MF: Cleavage of type I procollagen by human mast cell chymase initiates collagen fibril formation and generates a unique carboxyl-terminal propeptide. J Biol Chem 1997; 272: 7127-7131. – reference: 21. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, Tsujinoue H, Hukui H: Angiotensin-II type 1 recepter interaction is a major regulator for liver fibrosis development in rats. Hepatology 2001; 34: 745-750. – reference: 8. Algermissen B, Hermes B, Feldmann-Boeddeker I, Bauer F, Henz BM: Mast cell chymase and tryptase during tissue turnover: analysis on in vitromitogenesis of fibroblast and alterations in cutaneus scars. Exp Dermatol 1999; 8: 193-198. |
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| Snippet | ヒト循環血中でのアンジオテンシンI(AI)からアンジオテンシンII(AII)への変換は, その大部分がアンジオテンシン変換酵素(ACE)に依存している. ところが, ACEによらないA II産生経路があり, それにセリンプロテアーゼが関与することが証明されている1. セリンプロテアーゼの一つであるキマーゼは,... |
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| Title | 肝疾患とキマーゼ |
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