Prevention of normal tissue damage caused by primed neutrophils under the control of intracellular signal transduction

预防细胞内信号转导控制下引发的中性粒细胞引起的正常组织损伤

• 批准号: 09670797
• 负责人: YASUI Kozo
• 金额: $ 2.18万
• 依托单位: SHINSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670797/
• 关键词: neutrophils; eosinophils; GM-CSF; apoptosis; theophylline; Down syndrome; pentoxifylline; Behcet disease; 好酸球f; アポートーシス; 食細胞; 細胞内情報伝達; 炎症; 喘息; 活性酸素

In iniflammatory sites, GM-CSF is mainly produced by macrophages and activated T cells. The inflammatory site is surrounded by macrophages and T cells, which are called satelite cells. Bactericidal ability of neutrophils is augmented and the cellular survival is prolonged by the treatment of GM-CSF.In contrast, G-CSF has a weaker effect, G-CSF is mainly produced by epithelium or fibroblast in stromal cells. The lower concentrations of GM-CSF enhance neutrophil chemotaxis, meanwhile the higher concentrations of GM-CSF induce the tight regulation of integrin adhesiveness and the specific localization of activated neutrophils to inflammatory sites. From these findings, GM-CSF is supposed to play as a pro-inflammatory cytokine in several diseases as ARDS and bronchial asthma.The unnecessary prolongation of neutrophil and augmentation of bactericidal ability may produce toxic substances. The regulation of granulocyte life and function has been proposed as a key mechanism for the inhibition … More of inflammatory disease and tissue damage. In bronchial asthma, cytokines as GM-CSF and IL-5 are upregulated and have been proposed to cause granulocyte infilitration in the airway. We examined the abilities of theophylline, a brochodilator, to counteract the prolongation of human granulocyte survival caused by GM-CSF and IL-5. Theophylline's effect to accelerate granulocyte apoptosis is an important immunomodulatory action in the control of bronchial asthma. In addition, we examined neutrophil apoptosis in individuals with Down syndrome (DS). Granulocyte survival is shortened in DS individuals, accerelated apoptosis of granulocytes may be a factor to prevent chronic airway inflammation and bronchial asthma in DS.The superoxide dismutase gene resides on chromosome 21, SOD may be a key enzyme in the mechanism to induce cellular apoptosis.Behcet disease is a chronic condition in which the functions of neutrophils are characteristically increased. We examined the effect of pentoxifylline (a membrane fluidizer) in controlling Behcet disease, and further studies have been done between children's cases. Less

在炎症部位，GM-CSF主要由巨噬细胞和活化的T细胞产生。炎症部位被称为卫星细胞的巨噬细胞和T细胞包围。GM-CSF可增强中性粒细胞的杀菌能力，延长细胞存活时间，但作用较弱，主要由上皮细胞或基质细胞中的成纤维细胞产生。较低浓度的GM-CSF可增强中性粒细胞的趋化性，而较高浓度的GM-CSF可诱导整合素β的严格调节和活化的中性粒细胞向炎症部位的特异性定位。由此可见，GM-CSF可能在ARDS、支气管哮喘等疾病中起促炎细胞因子的作用，中性粒细胞不必要的延长和杀菌能力的增强可能产生毒性物质。粒细胞生命和功能的调节已被认为是抑制的关键机制 ...更多信息 炎症性疾病和组织损伤的风险在支气管哮喘中，细胞因子如GM-CSF和IL-5被上调，并且已被提出引起气道中的粒细胞浸润。我们研究了茶碱（一种支气管扩张剂）对抗GM-CSF和IL-5引起的人粒细胞存活延长的能力。茶碱促进粒细胞凋亡是其在支气管哮喘防治中的重要免疫调节作用。此外，我们还研究了唐氏综合征（DS）患者的中性粒细胞凋亡。DS患者粒细胞存活时间缩短，加速相关的粒细胞凋亡可能是预防DS患者慢性气道炎症和支气管哮喘的一个因素。超氧化物歧化酶（SOD）基因位于21号染色体上，SOD可能是诱导细胞凋亡的关键酶。我们检查了喷替福林（一种膜流化剂）在控制白塞氏病中的作用，并在儿童病例之间进行了进一步的研究。少

项目成果

I.Hu B, Yasui K.: "Effects of colony-stimulating factors (CSFs) on neutrophil apoptosis : possible roles in inflammation site." Int J Hematol. 66. 179-188 (1997)

I.Hu B、Yasui K.：“集落刺激因子 (CSF) 对中性粒细胞凋亡的影响：在炎症部位的可能作用。”

安井耕三, 小宮山淳: "Chediak-Higash : 症候群の責任遺伝子" 医学のあゆみ. 180. 510-511 (1997)

Kozo Yasui，Jun Komiyama：“Chediak-Higash：导致该综合征的基因”《医学史》180. 510-511 (1997)。

安井耕三: "Chediak-東症候群における責任蛋白質." 医学のあゆみ. 182. 767-770 (1997)

Kozo Yasui：“Chediak-Higashi 综合征中的责任蛋白。”医学史 182. 767-770 (1997)

Yasui K,Hu B,Nakazawa T,Agematsu K,Komiyama A.: "Theophylline accelerates granulocyte apoptosis not via phosphodiesterase inihibition" J Clin Invest. 100. 1677-1684 (1997)

Yasui K、Hu B、Nakazawa T、Agematsu K、Komiyama A.：“茶碱不是通过磷酸二酯酶抑制来加速粒细胞凋亡”J Clin Invest。

Nagumo H,Agematsu K,Shinozaki K,Hokibara S,Ito S,Takamoto M,Nikaido T,Yasui K,Uehara Y,Yachie A,Komiyama A: "CD27/CD70 interaction augments IgE secretion by promoting the differentiation of memory B cells into plasma cells" J Immunol. 161. 6496-6502 (1998

Nagumo H、Agematsu K、Shinozaki K、Hokibara S、Ito S、Takamoto M、Nikaido T、Yasui K、Uehara Y、Yachie A、Komiyama A：“CD27/CD70 相互作用通过促进记忆 B 细胞分化为 IgE 分泌，从而增强 IgE 分泌。