2000 年度実績報告書

血管炎症候群の分子メカニズムの解析と新たな病理形態学的基盤の確立

研究課題

研究課題/領域番号	11307003
研究機関	愛媛大学
研究代表者	能勢眞人愛媛大学, 医学部, 教授 (70030913)
研究分担者	沼野藤夫東京医科歯科大学, 医学部, 教授 (40013958) 居石克夫九州大学, 大学院・医学研究科, 教授 (70108710) 吉木敬北海道大学, 医学部, 教授 (60220612) 油谷親夫国立循環器病センター, 臨床検査部, 部長宮地良樹京都大学, 大学院・医学研究科, 教授 (30127146)
キーワード	原発性肺高血圧 / 高安動脈炎 / ANCA / HTLV-1 / HCMV / MPO / 血管炎感受性遺伝子 / CD72
研究概要	近年の血管細胞生物学の進歩と、血管炎症候群の病理や発症機構における問題点とのギャップは大きく、これを埋めてゆくための統合的な研究を昨年度に引き続き行い、今年度は特に以下の新たな成果を得た。 1)宿主の血管障害機構については、原発性肺高血圧での肺動脈叢状血管症の成り立ちに血管炎が関与する事実を明らかにし(由谷)、高安動脈炎の一部に抗MPO抗体が関与する可能性(中林)、大型血管炎にウイルスによるvasa vasorumの血管炎が関与する可能性(沼野)、結節性多発動脈炎を主とする膠原病における肝内血管炎の発症頻度(松本)、ANCA関連血管炎症候群の肺開胸生検例(能勢)を解析した。 2)モデル動物による解析では、HTLV-I env-pX遺伝子導入ラットの血管炎発症における胸腺間質細胞の重要性(吉木)、HCMV前早期発現遺伝子を血管壁に特異的に発現するトランスジェニックマウスや、新たに作出した組換えセンダイウイルスベクターの有用性(居石)を示した。また、MRL/lprマウスへのIRF-1遺伝子の導入による血管炎発症抑制機序(能勢)、MPOノックアウトマウスを用いての川崎病モデル(本症患児由来C.albicans菌体抽出物で誘導される血管炎)(直江)を解析した。また、新生血管先端の三次元構造を解析する新たな方法を開発した(藤原)。 4)ゲノム解析では、MRL/lprマウスの血管感受性遺伝子座をマップし、その位置的候補疾患遺伝子としてCD72 cDNA多型を明らかにし、また、血管炎における血管キャリバー特異的な遺伝子座の存在を示した(能勢)。 6)International Workshop on Systemic Vasculitis 2000を平成12年10月14日東京にてMolecular and Pathomorphological Bases on Vasculitis Syndromesをテーマに開催した。

研究成果
(25件)

すべてその他

すべて文献書誌 (25件)

[文献書誌] Nose M,Nishihara M,Kamogawa J,Terada M,Nakaturu S.: "Genetic basis of autoimmune disease in MRL/lpr mice : dissection of the complex pathological manifestations and their susceptibility loci."Immunogenetics. 2. 154-164 (2000)
[文献書誌] Nose M,Nishihara M,Fujii H: "Genetic basis of the complex pathological manifestations of collagen disease : Lessons from MRL/lpr and related mouse models."Int Rev Immunol. 19. 473-498 (2000)
[文献書誌] Nose M,Terada M,Nishihara M,Kamogawa J,Miyazaki T,Qu WM,Mori S,Nakatsuru S.: "Genome analysis of collagen disease in MRL/lpr mice : polygenic inheritance resulting in the complex pathological manifestations."Int J Cardiol. 75. S53-S61 (2000)
[文献書誌] 能勢眞人: "膠原病の病像多様性・類似性の起源-モデルマウスに学ぶゲノム病理学"リウマチ. 40. 833-848 (2000)
[文献書誌] Ito MR,Terasaki S,Kondo E,Shiwaku H,Fukuoka Y,Nose M.: "Experimental lupus nephritis in severe combined immunodeficient (SCID) mice : remodeling of the glomerular lesions by bystanderIgM antibodies."Clin Exp Immunol. 119. 340-345 (2000)
[文献書誌] Qu WM,Miyazaki T,Terada M,Lu LM,Nishihara M,Yamada A,Mori S,Nakamura Y,Ogasawara H,Yazawa C,Nakatsuru S,Nose M.: "Genetic dissection of vasculitis in MRL/lpr lupus mice : a novel susceptibility locus involving the CD72^c allele."Eur J Immunol. 30. 2027-2037 (2000)
[文献書誌] 能勢眞人: "膠原病の病像多様性・類似性の起源-モデルマウスのゲノム解析によるアプローチ"日病会誌. 89. 41-59 (2000)
[文献書誌] 石津明洋,吉木敬: "血管炎のモデル動物"最新医学. 55. 2611-2615 (2000)
[文献書誌] Inder SJ,Bobryshev YV,Cherian SM,Wang AY,Lord RSA,Masuda K,Yutani C.: "Immunophenotypic analysis of the aortic wall in Takayasu's arteritis : involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions."Cardiovas Surg. 8. 141-148 (2000)
[文献書誌] Inder SJ,Bobryshev YV,Cherian SM,Lord RSA,Masuda K,Yutani C: "Accumulation of lymphocytes, dendritic cells, and granulocytes in the aortic wall affected by Takayasu's disease."Angiol. 51. 565-579 (2000)
[文献書誌] Masaki I,Yonemitsu Y,Komori K,Ueno H,Nakashima Y,Nakagawa K,Fukumura M,Kato A,Hasan MK,Nagai Y,Sugimachi K,Hasegawa M,Sueishi K.: "Recombinant Sendai virus-mediated gene transfer to vasculature : a new class of efficient gene transfer vector to the vascular system."FASEB J. (in press).
[文献書誌] Egashira K,Koyanagi M,Kitamoto S,Weihua N,Kataoka C,Morishita R,Kaneda Y,Akiyama C,Nishida K,Sueishi K,Takeshita K.: "Anti-monocyte chemoattractant protein-1 gene therapy inhibits vascular remodeling in rats : blockade of MCP-1 activity after intramuscular transfer of a mutant gene inhibits vascular remodeling induced by chronic blockade of NO synthase."FASEB J. 14. 1974-1978 (2000)
[文献書誌] Yoshikawa H,Ishibashi T,Hata Y,Inomata H,Sueishi K.: "The suppressive effect of tecogalan sodium on in vitro angiogenesis via the periendothelial proteolytic activities."Ophthalmic Res. 32. 261-269 (2000)
[文献書誌] Nakagawa K,Chen Y-X,Ishibashi H,Yonemitsu Y,Murata T,Hata Y,Nakashima Y,Sueishi K.: "Angiogenesis and its regulation : roles of vascular endothelial cell growth factors."Semin Thromb Hemost. 26. 61-66 (2000)
[文献書誌] Ogishima D,Matsumoto T,Nakamura Y,Yoshida K,Kuwabara Y.: "Placental pathology in systemic lupus erythematosis with antiphospholipid antibodies."Pathol Int. 50. 224-229 (2000)
[文献書誌] Matsumoto T,Kobayashi S,Shimizu H,Nakajima M,Watanabe S,Kitami N,Sato N,Abe H,Aoki Y,Hoshi T,Hashimoto H.: "The liver in collagen disease : Pathologic study of 160 cases with particlar reference to primary biliary cirrosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver."Liver. 20. 366-373 (2000)
[文献書誌] Numano F,Kishi Y,Tanaka A,Ohkawara M,Kakuta T,Kobayashi Y.: "Inflammation and Atherosclerosis."Ann NY Acad Sci. 904. 65-76 (2000)
[文献書誌] Numano F.: "Vasa vasoritis, vasculitis and Atherosclerosis."Int J Cardiol. 75. 1-8 (2000)
[文献書誌] Kimura A,Ota M,Katsuyama Y,Ohbuchi N,Takahashi M,Kobayashi Y,Inoko H,Numano F.: "Mapping of the HLA-linked genes controlling the susceptibility to Takayasu's arteritis."Int J Cardiol. 75. 105-110 (2000)
[文献書誌] Numano F,Okawara M,Inomata H,Kobayashi Y.: "Takayasu's arteritis."Lancet. 356. 1023-1025 (2000)
[文献書誌] 沼野藤夫: "血管炎成因とその病態-特にvasa vasoritisの果たす役割について"脈管学. 40. 959-965 (2000)
[文献書誌] Nakabayashi K,Kamiya Y,Nagasawa T.: "Aortitis syndrome associated with positive perinuclear antineutrophil cytoplasmic antibody ; report of three cases."Int J Cardiol. 75. S89-S94 (2000)
[文献書誌] 中林公正: "ANCA関連疾患の臨床"日内会誌. 89. 520-523 (2000)
[文献書誌] Fujiwara T,Shimizu D,Kon K,Isshiki N,Tsunokuni H,and Aoyagi S: "A new method for detecting and localizing cell markers endocytosed by fibroblasts in epoxy resin semi-thin sections using scanning electron microscopy combined with energy dispersive X-ray microanalysis after ion-etching."J Electr Microsc. 49. 551-558 (2000)
[文献書誌] Shimizu D,Fujiwara T,Kon K,Issiki N,Tsunokuni H: "Three-dimensional reconstruction by scanning electron microscopy from serial epoxy resin semi-thin sections after ion-etching."J Electr Microsc. 50(in press).

2000 年度 実績報告書

血管炎症候群の分子メカニズムの解析と新たな病理形態学的基盤の確立

研究代表者

能勢 眞人 愛媛大学, 医学部, 教授 (70030913)

研究成果

[文献書誌] Nose M,Nishihara M,Kamogawa J,Terada M,Nakaturu S.: "Genetic basis of autoimmune disease in MRL/lpr mice : dissection of the complex pathological manifestations and their susceptibility loci."Immunogenetics. 2. 154-164 (2000)

[文献書誌] Nose M,Nishihara M,Fujii H: "Genetic basis of the complex pathological manifestations of collagen disease : Lessons from MRL/lpr and related mouse models."Int Rev Immunol. 19. 473-498 (2000)

[文献書誌] Nose M,Terada M,Nishihara M,Kamogawa J,Miyazaki T,Qu WM,Mori S,Nakatsuru S.: "Genome analysis of collagen disease in MRL/lpr mice : polygenic inheritance resulting in the complex pathological manifestations."Int J Cardiol. 75. S53-S61 (2000)

[文献書誌] 能勢眞人: "膠原病の病像多様性・類似性の起源-モデルマウスに学ぶゲノム病理学"リウマチ. 40. 833-848 (2000)

[文献書誌] Ito MR,Terasaki S,Kondo E,Shiwaku H,Fukuoka Y,Nose M.: "Experimental lupus nephritis in severe combined immunodeficient (SCID) mice : remodeling of the glomerular lesions by bystanderIgM antibodies."Clin Exp Immunol. 119. 340-345 (2000)

[文献書誌] Qu WM,Miyazaki T,Terada M,Lu LM,Nishihara M,Yamada A,Mori S,Nakamura Y,Ogasawara H,Yazawa C,Nakatsuru S,Nose M.: "Genetic dissection of vasculitis in MRL/lpr lupus mice : a novel susceptibility locus involving the CD72^c allele."Eur J Immunol. 30. 2027-2037 (2000)

[文献書誌] 能勢眞人: "膠原病の病像多様性・類似性の起源-モデルマウスのゲノム解析によるアプローチ"日病会誌. 89. 41-59 (2000)

[文献書誌] 石津明洋,吉木敬: "血管炎のモデル動物"最新医学. 55. 2611-2615 (2000)

[文献書誌] Inder SJ,Bobryshev YV,Cherian SM,Wang AY,Lord RSA,Masuda K,Yutani C.: "Immunophenotypic analysis of the aortic wall in Takayasu's arteritis : involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions."Cardiovas Surg. 8. 141-148 (2000)

[文献書誌] Inder SJ,Bobryshev YV,Cherian SM,Lord RSA,Masuda K,Yutani C: "Accumulation of lymphocytes, dendritic cells, and granulocytes in the aortic wall affected by Takayasu's disease."Angiol. 51. 565-579 (2000)

[文献書誌] Yoshikawa H,Ishibashi T,Hata Y,Inomata H,Sueishi K.: "The suppressive effect of tecogalan sodium on in vitro angiogenesis via the periendothelial proteolytic activities."Ophthalmic Res. 32. 261-269 (2000)

[文献書誌] Nakagawa K,Chen Y-X,Ishibashi H,Yonemitsu Y,Murata T,Hata Y,Nakashima Y,Sueishi K.: "Angiogenesis and its regulation : roles of vascular endothelial cell growth factors."Semin Thromb Hemost. 26. 61-66 (2000)

[文献書誌] Ogishima D,Matsumoto T,Nakamura Y,Yoshida K,Kuwabara Y.: "Placental pathology in systemic lupus erythematosis with antiphospholipid antibodies."Pathol Int. 50. 224-229 (2000)

[文献書誌] Numano F,Kishi Y,Tanaka A,Ohkawara M,Kakuta T,Kobayashi Y.: "Inflammation and Atherosclerosis."Ann NY Acad Sci. 904. 65-76 (2000)

[文献書誌] Numano F.: "Vasa vasoritis, vasculitis and Atherosclerosis."Int J Cardiol. 75. 1-8 (2000)

[文献書誌] Kimura A,Ota M,Katsuyama Y,Ohbuchi N,Takahashi M,Kobayashi Y,Inoko H,Numano F.: "Mapping of the HLA-linked genes controlling the susceptibility to Takayasu's arteritis."Int J Cardiol. 75. 105-110 (2000)

[文献書誌] Numano F,Okawara M,Inomata H,Kobayashi Y.: "Takayasu's arteritis."Lancet. 356. 1023-1025 (2000)

[文献書誌] 沼野藤夫: "血管炎成因とその病態-特にvasa vasoritisの果たす役割について"脈管学. 40. 959-965 (2000)

[文献書誌] Nakabayashi K,Kamiya Y,Nagasawa T.: "Aortitis syndrome associated with positive perinuclear antineutrophil cytoplasmic antibody ; report of three cases."Int J Cardiol. 75. S89-S94 (2000)

[文献書誌] 中林公正: "ANCA関連疾患の臨床"日内会誌. 89. 520-523 (2000)

[文献書誌] Shimizu D,Fujiwara T,Kon K,Issiki N,Tsunokuni H: "Three-dimensional reconstruction by scanning electron microscopy from serial epoxy resin semi-thin sections after ion-etching."J Electr Microsc. 50(in press).

2000 年度実績報告書

能勢眞人愛媛大学, 医学部, 教授 (70030913)