1989 Fiscal Year Annual Research Report

食品成分による生体防御の機作

Research Project

Project/Area Number	01636002
Research Institution	The University of Tokyo
Principal Investigator	多田富雄東京大学, 医学部, 教授 (10009136)
Co-Investigator(Kenkyū-buntansha)	栃倉辰六郎京都大学, 農学部, 教授 (70026524) 鈴木紘一東京都臨床医学総合研究所, 遺伝情報研究部, 部長 (80011948) 高久史磨東京大学, 医学部, 教授 (40048955) 上野川修一東京大学, 農学部, 教授 (50011945) 白井俊一順天堂大学, 医学部, 教授 (30115860)
Keywords	生体防御 / 免疫 / 消化管免疫 / 抗体 / リンパ球
Research Abstract	本研究では、食品成分の生体防御系に対する作用を、免疫応答系とそれ以外の作用を介した系で解析した。免疫応答系に関するものでは、無菌およびSPFマウスのパイエル板のTおよびB細胞について、フローサイトメトリーを行ない、消化管が免疫細胞分化の場として重要な役割を果していることを証明した。また代表的な牛乳アレルゲンであるαsl-カゼインを免疫したマウスより、Lytー2^+サプレッサ-T細胞をクローン化することに成功した。食品成分の自己免疫疾患におよぼす影響を検討した結果、低カロリー食がBWF_4マウスにおける自己免疫疾患の治療に効果のあることを立証した。さらに食品によるアレルギーの制御を目的として、患者に造血因子GCSFを投与すると、好中球数が増加することを明らかにした。また、生体の防御ポテンシャルを増強する目的で、ハイブリドーマを検定細胞として、食品中に抗体産生を促進する成分を検索し、卵黄リポタンパク質、スキムミルク、ラクトフェリンなどにその効果のあることを明らかにした。つぎに、好中球、マクロファージなどの白血球の局部浸潤を調べる方法を用い、植物性食品を中心に、免疫賦活作用を持つ成分を検索し、キノコ類、緑黄野菜類にその活性のあることを明らかにした。一部にはインターフェロン誘導活性がみられた。免疫系以外による生体防御では次のような成果が得られている。セノバイオティクス(有機人工成分)の解毒、排泄に必須である肝薬物代謝物質の誘導に食餌タンパク質の量、質が大きく影響することを明らかにした。また生体防御において重要な役割を果たしているビフィズス菌の増殖因子であるβーDフコシルグルコースを酵素的に合成した。さらに、生体防御系に重要な役割を果たしているカルシウムプロテアーゼについて、その構造と機能について分子生物学的研究が行なわれた。さらに、消化管に分布する免疫細胞の組織化学的特徴を解明した。

Research Products
(30 results)

All Other

All Publications (30 results)

[Publications] Nakayama,T.: "Biochemical identification of I-J as a novel dimeric surface molecule on mouse helper and suppressor T cell clones." International Immunology. 1. 50-58 (1989)
[Publications] Furutani,M.: "Post-transcriptional allelic exclusion of two functionally rearranged T-cell receptor α genes." International Immunology. 1. 281-288 (1989)
[Publications] Utsunomiya,N.: "Unidirectional inhibition of early signal transduction of helper T cells by cloned suppressor T cells." International Immunology. 1. 460-463 (1989)
[Publications] Horiuchi,T.: "Epitope specific regulation of the antibody response against α-lactoalbumins in tne mouse." Int.Archs.Allergy Appl.Immunol.(1990)
[Publications] Sekigawa,L.: "B cell hyper-responsiveness to IL2 and the age-associated decline in murine lupus." Clin.Immunol.Immujopatnol.51. 172-184 (1989)
[Publications] Hasegawa,K.: "Are Ly1 B cells responsible for the IL-2hyperresponsiveness of B cells in autoimmune-prone KZB×NZW F_1 mice." International Immunology. 1. 99-101 (1989)
[Publications] Ogai,M.: "Establishment of two distinct monoclonal natural thymocytotoxic autoantibodies(NTA)from New Zealand mice." Clin.Immunol.Immunophathol.53. 475-487 (1989)
[Publications] Abe,M.: "The novel murine B cell differentiation antigen Lp-3." International Immunology. 1. 576-581 (1989)
[Publications] Shirai,T.: "The expanded populations of CD4^-CD8-/+T cells associated with the lpr and pld mutations are CD2^-." Journal of Immunology. (1990)
[Publications] Okada,T.: "Distinct surface phenotype of B cells responsible for spontaneous production of IgM and IgG anti-DNA antibodies in autoimmume-prone NZB×NZW Fl mice." Autoimmunity. (1990)
[Publications] Kaminogawa,S.: "Application of monoclonal antibody to a comparative study of α-lactoalbumins from various species." J.Dairy Sci.72. (1989)
[Publications] Azuma,N.: "Presence of cell growth promoting peptides in chicken egg white extract." Agric.Biol.Chem.53. 1291-1295 (1989)
[Publications] Ametani,A.: "Structure of αsl-casein at an oil/water interface:an analytical approach using immunochemical methods." Agric.Biol.Chem.53. 1257-1300 (1989)
[Publications] Kaminogawa,S.: "Monoclonal sntibodies as probes for monitoring the denaturation process of bovine β-lactoglobulin." Biochem.Boiphys.Acta. 998. 50-56 (1989)
[Publications] Takahashi,T.: "Comparison between the antigenicity of native and unfolded β-lactoglobulin." Agric.Biol.Chem.(1990)
[Publications] Sato,S.: "Stimulation of monoclonal antibody production by human-human hybridoma cells with an elevated concentration of potassium or sodium phosphate in serum-free medium." Cytotechnology. 2. 63-67 (1989)
[Publications] Shirahata,S.: "DNA breakage by flavan 3-pls and procyanidins in the presence pf cupric ion." J.Agric.Food.Chem.37. 299-303 (1989)
[Publications] Yamada,K.: "Partial purification and characterization of immunoglobulin production stumulating factor derived from Namalwa cells." In Vitro Cell.Develop.Biol.25. 243-247 (1989)
[Publications] Murakami,H.: "Engeneered human antibodies with dual specificities." Highlights Modern Biochem.2. 1351-1360 (1989)
[Publications] Yamada,K.: "Screening of immunoglobulin production stimulating factor(IPSF)in foodstuffs using human-human hybridoma HB4C5 cells in serumfree medium." Agric.Biol.Chem.53. 2987-2991 (1989)
[Publications] Kubo,K.: "A novel yeast gene coding for a putative protein kinase." Gene. 76. 177-180 (1989)
[Publications] Konno,Y.: "Enzymatic properties of a novel phorbol ester receptor protein kinase,nPKC." J.Biochem.106. 673-678 (1989)
[Publications] Homma,Y.: "Tissue and cell type-specific expression of mRNAs for four types of inositol phospholipid-specific phospholipase C." Biochem.Biophys.Res.Commun.164. 400-412 (1989)
[Publications] Wada,H.: "Cell type-specific expression of the genes for the protein kinase C family:down regulation of mRNA for PKC alpha and nPKC epsilon." Biochem.Biophys.Res.Commun.165. 533-538 (1989)
[Publications] Emori,Y: "A second type of rat phospholinositide-specific phospholipase C containing a SRC related sequence not essential for phosphoinositis-hydrolyzing activity." J.Biol.Chem.264. 21855-21890 (1989)
[Publications] Hoio,F.: "Effect of dietary ascorbic acid,cholesterol and PCB on cholesterol and bile acid metabolism in a rat mutant unable to synthesize ascorbic acid." J.Nutrition. 119. 409-415 (1989)
[Publications] Oda,H.: "Effect of dietary methionine and polychlorinated biphernyls on cholesterol metabolism in rats fed a diet containing soy protein isolate." J.Nutr.Sci.Vitaminol.35. 333-348 (1989)
[Publications] Hayase,K.: "Effect of glucagon treatment on turnover of tissue proteins in rats." Nutr.Rep.International. 39. 605-615 (1989)
[Publications] Aoyama,Y.: "Effect on lipids in liver and serum,and some urinary components pf dietary supplement of excess lysine given to previously starved or non-starved rats." Agric.Biol.Chem.53. 2461-2468 (1989)
[Publications] Aoyama,Y.: "Effect of dietary supplement of excess histidine on liver lipids and serum cholesterol in rats fed diets varying in casein levels and protein quality." Nutr.Rep.International. 39. 1183-1193 (1989)

1989 Fiscal Year Annual Research Report

食品成分による生体防御の機作

Principal Investigator

多田 富雄 東京大学, 医学部, 教授 (10009136)

Research Products

[Publications] Nakayama,T.: "Biochemical identification of I-J as a novel dimeric surface molecule on mouse helper and suppressor T cell clones." International Immunology. 1. 50-58 (1989)

[Publications] Furutani,M.: "Post-transcriptional allelic exclusion of two functionally rearranged T-cell receptor α genes." International Immunology. 1. 281-288 (1989)

[Publications] Utsunomiya,N.: "Unidirectional inhibition of early signal transduction of helper T cells by cloned suppressor T cells." International Immunology. 1. 460-463 (1989)

[Publications] Horiuchi,T.: "Epitope specific regulation of the antibody response against α-lactoalbumins in tne mouse." Int.Archs.Allergy Appl.Immunol.(1990)

[Publications] Sekigawa,L.: "B cell hyper-responsiveness to IL2 and the age-associated decline in murine lupus." Clin.Immunol.Immujopatnol.51. 172-184 (1989)

[Publications] Hasegawa,K.: "Are Ly1 B cells responsible for the IL-2hyperresponsiveness of B cells in autoimmune-prone KZB×NZW F_1 mice." International Immunology. 1. 99-101 (1989)

[Publications] Ogai,M.: "Establishment of two distinct monoclonal natural thymocytotoxic autoantibodies(NTA)from New Zealand mice." Clin.Immunol.Immunophathol.53. 475-487 (1989)

[Publications] Abe,M.: "The novel murine B cell differentiation antigen Lp-3." International Immunology. 1. 576-581 (1989)

[Publications] Shirai,T.: "The expanded populations of CD4^-CD8-/+T cells associated with the lpr and pld mutations are CD2^-." Journal of Immunology. (1990)

[Publications] Okada,T.: "Distinct surface phenotype of B cells responsible for spontaneous production of IgM and IgG anti-DNA antibodies in autoimmume-prone NZB×NZW Fl mice." Autoimmunity. (1990)

[Publications] Kaminogawa,S.: "Application of monoclonal antibody to a comparative study of α-lactoalbumins from various species." J.Dairy Sci.72. (1989)

[Publications] Azuma,N.: "Presence of cell growth promoting peptides in chicken egg white extract." Agric.Biol.Chem.53. 1291-1295 (1989)

[Publications] Ametani,A.: "Structure of αsl-casein at an oil/water interface:an analytical approach using immunochemical methods." Agric.Biol.Chem.53. 1257-1300 (1989)

[Publications] Kaminogawa,S.: "Monoclonal sntibodies as probes for monitoring the denaturation process of bovine β-lactoglobulin." Biochem.Boiphys.Acta. 998. 50-56 (1989)

[Publications] Takahashi,T.: "Comparison between the antigenicity of native and unfolded β-lactoglobulin." Agric.Biol.Chem.(1990)

[Publications] Sato,S.: "Stimulation of monoclonal antibody production by human-human hybridoma cells with an elevated concentration of potassium or sodium phosphate in serum-free medium." Cytotechnology. 2. 63-67 (1989)

[Publications] Shirahata,S.: "DNA breakage by flavan 3-pls and procyanidins in the presence pf cupric ion." J.Agric.Food.Chem.37. 299-303 (1989)

[Publications] Yamada,K.: "Partial purification and characterization of immunoglobulin production stumulating factor derived from Namalwa cells." In Vitro Cell.Develop.Biol.25. 243-247 (1989)

[Publications] Murakami,H.: "Engeneered human antibodies with dual specificities." Highlights Modern Biochem.2. 1351-1360 (1989)

[Publications] Yamada,K.: "Screening of immunoglobulin production stimulating factor(IPSF)in foodstuffs using human-human hybridoma HB4C5 cells in serumfree medium." Agric.Biol.Chem.53. 2987-2991 (1989)

[Publications] Kubo,K.: "A novel yeast gene coding for a putative protein kinase." Gene. 76. 177-180 (1989)

[Publications] Konno,Y.: "Enzymatic properties of a novel phorbol ester receptor protein kinase,nPKC." J.Biochem.106. 673-678 (1989)

[Publications] Homma,Y.: "Tissue and cell type-specific expression of mRNAs for four types of inositol phospholipid-specific phospholipase C." Biochem.Biophys.Res.Commun.164. 400-412 (1989)

[Publications] Wada,H.: "Cell type-specific expression of the genes for the protein kinase C family:down regulation of mRNA for PKC alpha and nPKC epsilon." Biochem.Biophys.Res.Commun.165. 533-538 (1989)

[Publications] Emori,Y: "A second type of rat phospholinositide-specific phospholipase C containing a SRC related sequence not essential for phosphoinositis-hydrolyzing activity." J.Biol.Chem.264. 21855-21890 (1989)

[Publications] Hoio,F.: "Effect of dietary ascorbic acid,cholesterol and PCB on cholesterol and bile acid metabolism in a rat mutant unable to synthesize ascorbic acid." J.Nutrition. 119. 409-415 (1989)

[Publications] Oda,H.: "Effect of dietary methionine and polychlorinated biphernyls on cholesterol metabolism in rats fed a diet containing soy protein isolate." J.Nutr.Sci.Vitaminol.35. 333-348 (1989)

[Publications] Hayase,K.: "Effect of glucagon treatment on turnover of tissue proteins in rats." Nutr.Rep.International. 39. 605-615 (1989)

[Publications] Aoyama,Y.: "Effect on lipids in liver and serum,and some urinary components pf dietary supplement of excess lysine given to previously starved or non-starved rats." Agric.Biol.Chem.53. 2461-2468 (1989)

[Publications] Aoyama,Y.: "Effect of dietary supplement of excess histidine on liver lipids and serum cholesterol in rats fed diets varying in casein levels and protein quality." Nutr.Rep.International. 39. 1183-1193 (1989)

多田富雄東京大学, 医学部, 教授 (10009136)