研究者詳細 - 水野　正司

論文 - 水野　正司

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【特集:これだけは知っておきたい分子腎臓学2007】 C5a. 招待有り

水野正司、湯澤由紀夫、松尾清一

腎と透析 63 巻頁： 580-582 2007年

Complement membrane attack is required for endplate damage and clinical disease in passive experimental myasthenia gravis in Lewis rats 査読有り国際共著国際誌

J. Chamberlain-Banoub, J. W. Neal, M. Mizuno, C. L. Harris, B. P. Morgan

CLINICAL AND EXPERIMENTAL IMMUNOLOGY 146 巻 ( 2 ) 頁： 278 - 286 2006年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BLACKWELL PUBLISHING

Myasthenia gravis (MG) is a debilitating and potentially fatal neuromuscular disease characterized by the generation of autoantibodies reactive with nicotinic acetylcholine receptors (AChR) that cause loss of AChR from the neuromuscular endplate with resultant failure of neuromuscular transmission. A role for complement (C) in the pathology of human MG has been suggested based upon identification of C activation products in plasma and deposited at the endplate in MG. In the rat model, experimental autoimmune MG (EAMG), C depletion or inhibition restricts clinical disease, further implicating C in pathology. The mechanisms by which C activation drives pathology in MG and EAMG are unclear. Here we provide further evidence implicating C and specifically the membrane attack complex (MAC) in the Lewis rat passive EAMG model of MG. Rats deficient in C6, an essential component of the MAC, were resistant to disease induction and endplate destruction was reduced markedly compared to C6-sufficient controls. After reconstitution with C6, disease severity and endplate destruction in the C6-deficient rats was equivalent to that in controls. The data confirm the essential role of the MAC in the destruction of the endplate in EAMG and raise the prospect of specific MAC inhibition as an alternative therapy in MG patients resistant to conventional treatments.

DOI： 10.1111/j.1365-2249.2006.03198.x

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The membrane attack pathway of complement drives pathology in passively induced experimental autoimmune myasthenia gravis in mice 査読有り国際共著国際誌

B. P. Morgan, J. Chamberlain-Banoub, J. W. Neal, W. Song, M. Mizuno, C. L. Harris

CLINICAL AND EXPERIMENTAL IMMUNOLOGY 146 巻 ( 2 ) 頁： 294 - 302 2006年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BLACKWELL PUBLISHING

The human neuromuscular disease myasthenia gravis (MG) is characterized by the generation of autoantibodies reactive with nicotinic acetylcholine receptors (AChR) that cause loss of AChR from the neuromuscular end-plate with resultant failure of neuromuscular transmission. A role for complement (C) in AChR loss has been suggested based uponmorphological identification of C at the end-plate in MG and from the effects of C inhibition in murine models. Here we provide further evidence implicating C, and specifically the membrane attack complex (MAC), in a mouse model of MG. Mice deficient in the C regulators Daf1 and/or Cd59a were tested in the model. Wild-type mice were resistant to disease while mice deficient in Daf1 had mild disease symptoms with evidence of C activation and AChR loss at end-plates. Cd59a-deficient mice had very mild disease with some muscle inflammation and essentially undamaged end-plates. In contrast, mice deficient in both C regulators developed a severe paralytic disease with marked muscle inflammation and loss of end-plates. Inhibition of MAC assembly abrogated clinical disease in these double-deficient mice, demonstrating conclusively that MAC formation was driving pathology in the model. These findings provoke us to suggest that current anti-C therapeutics targeting MAC assembly will be beneficial in MG patients resistant to conventional therapies.

DOI： 10.1111/j.1365-2249.2006.03205.x

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Spermatogenic cells distal to the blood-testis barrier in rats lack C3 convertase regulators and may be at risk of complement-mediated injury.

Mizuno M, Harris CL, Morgan BP

Journal of reproductive immunology 69 巻 ( 1 ) 頁： 23 - 34 2006年2月

Complement and complement regulators in the male reproductive system. 査読有り国際共著国際誌

Harris CL, Mizuno M, Morgan BP

Molecular immunology 43 巻 ( 1-2 ) 頁： 57 - 67 2006年1月

Stage-specific expression of CD55 isoforms during spermiogenesis in the rat

Mizuno, M; Harris, CL; Donev, RM; Spiller, OB; Morgan, BP

MOLECULAR IMMUNOLOGY 43 巻 ( 1-2 ) 頁： 156 - 156 2006年1月

The membrane attack pathway of complement drives pathology in experimental autoimmune myasthenia gravis in mice. 査読有り

Morgan BP., Chamberlain-Banoub J., Neal JW.,Song W., Mizuno M., Harris CL.

Clin Exp Immunol 146 巻頁： 294-302 2006年

Complement and complement regulators in the male reproductive system. 招待有り査読有り

Harris CL., Mizuno M., Morgan BP.

Mol Immunol 43 巻頁： 57-67 2006年

Complement membrane attack is required for endplate damage and clinical disease in experimental myasthenia gravis in Lewis rats. 査読有り

Chamberlain-Banoub J., Neal JW., Mizuno M., Harris CL., Morgan BP.

Clin Exp Immunol 146 巻頁： 278-286 2006年

CD55 expression in rat male reproductive tissue: Differential expression in testis and expression of a unique truncated isoform on spermatozoa. 査読有り

Mizuno M., Donev RM., Harris CL., Morgan BP.

Mol. Immunol. 44 巻頁： 1624-1633 2006年

A review of current knowledge of the complement system and the therapeutic opportunities in inflammatory arthritis. 招待有り査読有り

Mizuno M.

Curr Med Chem 13 巻頁： 1707-1717 2006年

Unique expression patterns of membrane complement regulators and C3 in rat testes and spermatozoa delineate the blood-testis barrier and suggest distinct functional roles in germ cell development. 査読有り

Mizuno M., Harris CL., Morgan BP.

J Reprod Immunol 69 巻頁： 23-34 2006年

Mizuno M, Harris CL, Morgan BP

J Reprod Immunol 69 巻頁： 23-34 2006年

Shiga toxin 1causes direct renal injury in rats 査読有り国際誌

Yamamoto ET, Mizuno M, Nishikawa K, Miyazawa S, Zhang LS, Matsuo S, Natori Y

INFECTION AND IMMUNITY 73 巻 ( 11 ) 頁： 7099 - 7106 2005年11月

Novel C5a regulators in inflammatory disease. 招待有り査読有り国際誌

Mizuno M, Cole DS

Expert opinion on investigational drugs 14 巻 ( 7 ) 頁： 807 - 821 2005年7月

Expression of CD46 in developing rat spermatozoa: ultrastructural localisation and utility as a marker of the various stages of the seminiferous tubuli. 査読有り

Mizuno M., Harris CL., Suzuki N., Matsuo S., Morgan BP.

Biol Reprod 72 巻頁： 908-915 2005年

Shiga toxin-1 causes direct renal injury in rats. 査読有り

Yamamoto ET., Mizuno M., Nishikawa K., Miyazawa S., Zhang L., Matsuo S., Natori Y.

Infect Immun 73 巻頁： 7099-7106 2005年

Novel C5a regulators in inflammation. 招待有り査読有り

Mizuno M., Cole DS.

Expert Opin Investig Drugs 14 巻頁： 807-821 2005年

CD59a is the primary regulator of membrane attack complex assembly in the mouse.

Baalasubramanian S, Harris CL, Donev RM, Mizuno M, Omidvar N, Song WC, Morgan BP

Journal of immunology (Baltimore, Md. : 1950) 173 巻 ( 6 ) 頁： 3684 - 92 2004年9月

Inummohistochemical analysis of membrane complement regulatory proteins in rat testis: unique roles for DAF and MCP in spermatozoal function?

Mizuno, M; Harris, CL; Morgan, BP

MOLECULAR IMMUNOLOGY 41 巻 ( 2-3 ) 頁： 280 - 280 2004年6月

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