Analysis of leukocyte of rejection mechanism of early stage of islets transplantation.

• Project/Area Number: 19591192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Fukuoka University
• Principal Investigator: ANZAI Keizo Fukuoka University, 医学部, 講師 (60258556)
• Co-Investigator(Kenkyū-buntansha): YASUNAMI Youichi 福岡大学, 医学部, 教授 (00166521) ; KOGAWA Kazuhiko 福岡大学, 医学部, 助教 (60360301) ; MATSUOKA Nobuhide 福岡大学, 医学部, 助教 (40461503)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 移植・再生医療 / 1型糖尿病 / 免疫学 / 膵島移植 / レーザーマイクロダイゼクション / 早期拒絶反応 / ケモカイン

Research Abstract

(1)1型糖尿病のモデル動物であるNODマウスを用いて、Laser Microdissection (LMD)法による膵島浸潤リンパ球の解析を行い、膵島破壊につながるTh2からTh1への変化は局所の膵島炎の進行度によるものではなく全身的にTh1優位に傾ける因子により変化すると考えられた。また顎下腺でも膵島と同様のTh1/Th2バランス変化が認められたことから、膵島と同様な破壊機序が存在すると考えられた。LMD法による凍結切片中の細胞の解析は確立している。
(2)同様の方法を用いて肝臓内移植膵島の移植後6時間以内の早期拒絶機序における白血球を経時的に採取しLMD法を回収しどのような細胞がケモカインを産生しているか、その機序を解析中である。
(3)肝臓内移植膵島早期拒絶機序には移植膵島から放出されるHMGB1が引き金となり、HMGB1により肝内単核球、NKT白血球からのIFN-γ、IL-12、IL-6産生が増強され膵島は破壊される。さらにTHR-2,RAGEがHMGB1の受容体であることが解明した。

Research Products

• [Journal Article] Adverse effects of obesity on β-cell function in Japanese subjects wity normal glucose tolerance (2008)
  • Author(s): Akehi Y, Anzai K, Katsua H, Yoshida R, Ohkubo K, Yamashita T, Kawashima H, Ono J.
  • Journal Title: Obesity Research & Clinical Practice 2(3) Pages: 195-202
• [Journal Article] The immunoregulatory role of NKT cells in cyclophosphamide-induced tolerance. (2007)
  • Author(s): Iwai T, Tomita Y, Kajiwara T, Onzuka T, Okano S, Yasunami Y, Yoshikai Y, Nomoto K, Tominaga R.
  • Journal Title: Transplantation 84(12) Pages: 1686-95
• [Journal Article] Effects of cyclosporin A on the activation of NKT cells induced by α-galactosylceramide. (2007)
  • Author(s): Kajiwara T, Tomita Y, Okano S, Iwai T, Yasunami Y, Yoshikai Y, Nomoto K, Tominaga R, Yasui H.
  • Journal Title: Transplantation 83 Pages: 184-192
• [Journal Article] Beta-cell function is a major contributor to oral glucose disposition in obese Japanese students. (2007)
  • Author(s): Asano T, Yoshida R, Ogata H, Kogawa K, Ogimoto M, Akehi Y, Anzai K, Ono J, Tamura K, Hidehira K, Kikuchi M.
  • Journal Title: Endocr J. 54(6) Pages: 903-910
  • NAID: 130004443341
• [Journal Article] The effects of age on insulin sensitivity and insulin secretion in Japanese subjects with normal glucose tolerance. (2007)
  • Author(s): Akehi Y, Oketa A, Mitsuyoshi Y, Yoshida R, Ohkubo K, Yamashita T, kawashima H, Anzai K, Ono J.
  • Journal Title: Rinsho Byori. 55(10) Pages: 901-905
  • NAID: 10020165140
• [Journal Article] Characteristic Features of Metabolic Syndrome in Obese Japanese Students. (2007)
  • Author(s): Asano T, Yoshida R, Ogata H, Kogawa K, Akehi Y, Anzai K, Ono J, Tamura K, Kikuchi M.
  • Journal Title: Med. Bull. Fukuoka Univ. 34(3) Pages: 189-194
• [Journal Article] Successful Islet Transplantation to Two Recipients From a Single Donor by Targeting Proinflammatory Cytokines in Mice. (2007)
  • Author(s): Satoh M, Yasunami Y, Matsuoka N, Nakano M, Itoh T, Nitta T, Anzai K, Ono J, Taniguchi M, Ikeda S.
  • Journal Title: Transplantation 83(8) Pages: 1085-1092
• [Journal Article] Increased lipid absorption and transport in the small intestine of Zucker obese rats.
  • Author(s): Anzai K, Fukagawa K, Iwakiri R, Fujimoto K, Akashi K, Tso P.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition. (in press) Pages: 0-0
  • NAID: 130004466565
• [Journal Article] Prevention of early loss of transplanted islets in the liver of mice by adenosine.
  • Author(s): Nitta T, Itoh T, Matsuoka N, Mera T, Kojima D, Nakano M, Yamashita Y, Yasunami Y.
  • Journal Title: Transplantation (in press) Pages: 0-0
• [Presentation] Change in high molecular weight adiponectin and insulin resistance. (2009)
  • Author(s): Matono S, Yoshimura E, Kumahara K, Tobina T, Kushimizu T, Kiyonaga A, Anzai K, Tanaka T.
  • Organizer: 20th World Diabetes Congress.
  • Place of Presentation: Canada
• [Presentation] The influence of adipocytokines, muscle and hepatic lipid content on insulin resistance in Japanese. (2009)
  • Author(s): Yoshimura E, Kumahara H, Tobina T, Matono S, Kiyonaga A, Kimura M, Tsukikawa H, Kawano S, Etou T, Irie S, Anzai K, Tanaka H.
  • Organizer: 20th World Diabetes Congress.
  • Place of Presentation: Canada
• [Presentation] A novel mechanism involved in early loss of transplanted islets in the liver mediated by HMGB1. (2009)
  • Author(s): Itoh T, Nakagawa R, Matsuoka N, Nagata N, Nitta T, Mera T, Yamashita Y, Okamoto K, Yamamoto H, Yamada S, Maruyama I, Taniguchi M, Yasunami Y.
  • Organizer: 69th Scientific Sessions of American Diabetes Association.
  • Place of Presentation: New Orleans, USA.
• [Presentation] The Significance of b Cells in the Pathogenesis of type 1 Diabetes and a Possible Role of AIRE Gene. (2009)
  • Author(s): Matsuo T, Noguchi Y, Nagao Y, Shindo M, Kogawa K, Iwakiri R, Akashi T, Kondo S, Hara T, Kudoh J, Shimizu H, Kurisaki H, Katsuta H, Anzai K, Nagafuchi S.
  • Organizer: 69th Scientific Sessions of American Diabetes Association.
  • Place of Presentation: New Orleans, USA.
• [Presentation] Effect of exercise and diet intervention on the anthropometric measures and metabolic risk factors in Japanese. (2009)
  • Author(s): Yoshimura E, Kumahara H, Tobina T, Koshimizu T, Shindo M, Kiyonaga A, Anzai K, Tanaka H.
  • Organizer: European Congress on Obesity.
  • Place of Presentation: Switzerland.
• [Presentation] 腎移植後膵島移植を施行した1型糖尿病の経過報告 (2009)
  • Author(s): 安西慶三、明比祐子、中野真樹子、中野昌彦、松岡信秀、伊藤威、新田智之、米良利之、金城亜哉、小野順子、安波洋一
  • Organizer: 第52回日本糖尿病学会
  • Place of Presentation: 大阪
• [Presentation] 膵島移植の現状と展望 (2008)
  • Author(s): 安西慶三、中野昌彦、明比祐子、吉満研吾、松永彰、川島博信、金城亜哉、小野順子、安波洋一
  • Organizer: 第46回日本糖尿病学会九州地方会
  • Place of Presentation: 久留米
• [Presentation] Adenosine has an inhibitory effect on NKT cells facilitating to prevent early loss of transplanted islets in association with engraftments. (2008)
  • Author(s): T Nitta, N Matsuoka, T Itoh, T Mera, A Kinjo, M Nakano, Y Yamashita, Y Yasunami
  • Organizer: 22th International Congress of the Transplantation Society.
  • Place of Presentation: Sydney, Australia.
• [Presentation] 膵島移植の現状と展望 (2008)
  • Author(s): 安西慶三
  • Organizer: 第46会日本糖尿病学会九州地方会
  • Place of Presentation: 福岡県
• [Presentation] Adenosine has an inhibitory effect on NKT cells facilitating to prevent early loss of transplanted islets in association with engraftments. (2008)
  • Author(s): T. Nitta, N Matsuoka, Y Yasunami
  • Organizer: XXII International Congress of the Transplantation Society
  • Place of Presentation: Australia
• [Presentation] Timing of the Second Grafts Is Crucial in Sequential Islet Transplan-tation to Prevent Early Loss of Islets in the Liver of Mice in Relation to Induction of Hypo-Responsiveness of NKT Cells (2007)
  • Author(s): 松岡 信秀
  • Organizer: 第67回米国糖尿病会議
  • Place of Presentation: シカゴ/米国
  • Year and Date: 2007-06-24
• [Presentation] Successful islet transplantation from one donor to one recipient by targeting IL-6/IL-6 receptor signaling in mice. (2007)
  • Author(s): Itoh T, Matsuoka N, Nitta T, Nakano M, Mera T, Yamashita Y, Ono J, Yasunami Y.
  • Organizer: Joint Conference of Cell Transplantation Society International Pancreas and Islet Transplant Association and Xenotransplantation Association
  • Place of Presentation: Minneapolis, USA.
• [Presentation] Timing of the Second Grafts is Crucial in Sequential Islet Transplantations to Prevent Early Loss of Islets in the Liver of Mice in Relation to Induction of Hypo-responsiveness of NKT Cells. (2007)
  • Author(s): Matsuoka N, Itoh T, Nitta T, Nakano M, Anzai K, Ono J, Yuichi Y, Yamashita Y, Taniguchi M, Yasunami Y.
  • Organizer: 67th Scientific Sessions of American Diabetes Association.
  • Place of Presentation: Chicago, USA