Role of pertussis toxin subunits in the cell-adhesion and signal-transduction in mice

百日咳毒素亚基在小鼠细胞粘附和信号转导中的作用

• 批准号: 04454197
• 负责人: SATO Hiroko
• 金额: $ 0.9万
• 依托单位: National Institute of Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454197/
• 关键词: Pertussis toxin; Leukocytosis; Monoclonal antibody; Adhesion factor; Mouse encephalopathy; リンパ節細胞; 百白咳毒素; 白血球増夛症; セレクチン

Pertussis toxin consisting of five different subunits (S1-S5) induces diverse and unique biological activities in endocrine, immune, and nervous systems. The subunit structure of pertussis toxin (PT) is well defined, but a role of each subunit in the pathophysiological activities is still unclear. The ADP-ribosyl-transferase activity of the S1 to G-protein is essential for most of major biological or toxic activities of PT.Although the B oligomer (S2-S5) is known as a binding protein, the each subunit in the B oligomer must play rather complex roles to produce the various unique PT activities.In this study, roles of each subunit of PT as adhesin and signal transducer in leukocytosis promotion and encephalopathy induction were explored. For this purpose, the mouse monoclonal antibodies against each subunit of PT were utilized as a major powerful tool through the experiments. Leukocytosis caused by intravenous (iv) injection of PT was suppressed by administration of not only anti-S1 but … More also anti-B monoclonal antibodies even at three days after the iv injections. This results suggest that PT on acceptor cells is still able to interact with the antibody after the time when the leukocytosis already occurred and that unhoming leukocytes in the peripheral blood may be able to home by the PT-neutralization with the antibody. Similar results were obtained by the iv injection of lymphocytes treated with PT in vitro. Some preliminary experimental data are accumulating to investigate the interaction between the lymphocytes and endothelial cells of mice in vivo and in vitro. Further, encephalopathy and leukocytosis induced by the intracerebral (ic) injection of PT in mice were also neutralized with the antibody administered by iv injection, but some anti-S1 or anti-S2 antibodies which were not able to neutralize the leukocytosis inhibited the induction of the encephalopathy. The S2 and S3 seems to play different and specific role through adherence to cell receptors. And S4 may contribute to stabilization of some signal transduction to the cell membrane and translocation of active part of S1 to an active site at and/or after the binding step. Less

百日咳毒素由5个不同的亚基（S1-S5）组成，在内分泌、免疫和神经系统中诱导多种独特的生物活性。百日咳毒素（PT）的亚基结构已被很好地定义，但每个亚基在病理生理活动中的作用仍不清楚。虽然B寡聚体（S2-S5）被认为是一种结合蛋白，但B寡聚体中的每个亚基必须发挥相当复杂的作用才能产生各种独特的PT活性。探讨PT各亚基作为粘附素和信号转导子在白细胞增多和脑病诱导中的作用。为此目的，针对PT的每个亚基的小鼠单克隆抗体被用作通过实验的主要有力工具。静脉注射PT引起的白细胞增多不仅被抗S1抗体抑制， ...更多信息 甚至在静脉注射后三天也存在抗B单克隆抗体。该结果表明，在白细胞增多已经发生的时间之后，受体细胞上的PT仍然能够与抗体相互作用，并且外周血中的未归巢的白细胞可能能够通过与抗体的PT中和而归巢。静脉注射PT体外处理的淋巴细胞也得到类似的结果。小鼠淋巴细胞与内皮细胞在体内外相互作用的初步实验研究正在积累。此外，小鼠脑内（ic）注射PT诱导的脑病和白细胞增多也被静脉注射给药的抗体中和，但一些不能中和白细胞增多的抗S1或抗S2抗体抑制了脑病的诱导。S2和S3通过与细胞受体的粘附发挥不同的特异性作用。和S4可能有助于稳定一些信号转导到细胞膜和易位的活性部分的S1的活性位点在和/或之后的结合步骤。少

项目成果

Kaslow,H.: "Antibody inhibition of the ADP-ribosyltransferase activity of pertussis toxin." Biologicals. 21. 24-25 (1993)

Kaslow, H.：“百日咳毒素 ADP-核糖基转移酶活性的抗体抑制。”

Kaslow, H.and Sato, H.: "Antibody inhibition of the ADP-ribosyltransferase activity of pertussis toxin." Biologicals. 21. 24-25 (1993)

Kaslow, H. 和 Sato, H.：“百日咳毒素 ADP-核糖基转移酶活性的抗体抑制。”

Sato, Y.and Sato, H.: "Acellular pertussis vaccine as a solution to the prevention of whooping cough." Current Opinion in Infectious Diseases. 5. 399-405 (1992)

Sato, Y. 和 Sato, H.：“无细胞百日咳疫苗作为预防百日咳的解决方案。”

Sato, H.and Sato, Y.: "A role of pertussis toxin subunits in mouse encephalopathy." Microecology and Therapy. (in press).

Sato, H. 和 Sato, Y.：“百日咳毒素亚基在小鼠脑病中的作用。”

HIROKO SATO,YUJI SATO: "Structural relationship between the S1 and S4 subunits of pertussis toxin" FEMS microbiology letters. 115. 63-70 (1994)

HIROKO SATO、YUJI SATO：“百日咳毒素 S1 和 S4 亚基之间的结构关系”FEMS 微生物学快报。