The role of DAMPs on induction and termination of inflammatory responses induced by necrotic cells.

DAMP 在诱导和终止坏死细胞诱导的炎症反应中的作用。

• 批准号: 21590078
• 负责人: NAGATA Kisaburo
• 金额: $ 3万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590078/
• 关键词: 免疫学; necrosis; neutrophil; inflammation; chemokine; DAMPs

In order to examine the mechanism, we used an inflammation model induced by injection of several types of necrotic cells into the peritoneal cavity in this study. The injection of necrotic P388 cells(leukemia cells) and necrotic peritoneal neutrophils(necrotic activated neutrophils), which were obtained from the peritoneal cavity upon injection of thioglycollate broth, induced the infiltration of neutrophils and subsequently that of monocytes/macrophages, whereas the injection of necrotic thymocytes and necrotic bone marrow neutrophils(necrotic resting neutrophils) did not. These results suggested that the induction of inflammatory response induced by necrotic cells depend on the cell type undergoing necrosis. In agreement with induction of cell infiltration, the injection also induced the production of KC and MIP-2, and subsequently that of MCP-1 only when necrotic P388 cells or necrotic activated neutrophils were injected. Although the level of KC was higher than that of MIP-2, both anti-KC Ab and anti-MIP-2 Ab significantly inhibited the infiltration of neutrophils. These results indicate that KC and MIP-2 play important roles in the infiltration of neutrophils into the site of injection of necrotic cells.

为了研究其机制，我们在本研究中使用了通过将几种类型的坏死细胞注射到腹腔中诱导的炎症模型。注射坏死P388细胞（白血病细胞）和坏死腹膜中性粒细胞（坏死活化中性粒细胞）（在注射巯基乙酸盐肉汤后从腹膜腔获得）诱导中性粒细胞浸润，随后诱导单核细胞/巨噬细胞浸润，而注射坏死胸腺细胞和坏死骨髓中性粒细胞（坏死静息中性粒细胞）则不会。这些结果表明，坏死细胞诱导的炎症反应的诱导依赖于发生坏死的细胞类型。与细胞浸润的诱导一致，注射也诱导KC和MIP-2的产生，并且随后仅当注射坏死的P388细胞或坏死的活化的中性粒细胞时诱导MCP-1的产生。尽管KC的表达水平高于MIP-2，但抗KC抗体和抗MIP-2抗体均能显著抑制中性粒细胞的浸润。这些结果表明KC和MIP-2在中性粒细胞向坏死细胞注射部位的浸润中起重要作用。

项目成果

The importance of infiltrating neutrophils in SDF-1 production leading to regeneration of the thymus after whole-body X-irradiation.

• DOI: 10.1016/j.cellimm.2011.01.006
• 发表时间: 2011
• 期刊: Cellular immunology
• 影响因子: 4.3
• 作者: E. Nakayama;Y. Shiratsuchi;Yoshiro Kobayashi;K. Nagata

Apoptotic neutrophils and nitric oxide regulate cytokine production by IFN-g-stimulated macrophages

凋亡中性粒细胞和一氧化氮调节 IFN-g 刺激的巨噬细胞产生细胞因子

• 发表时间: 2011
• 期刊: Cytokine
• 影响因子: 3.8
• 作者: Shibata;T.;Nagata;K.;and Kobayashi;Y.
• 通讯作者: Y.

Effect of aging on inflammatory responses to necrotic cells

衰老对坏死细胞炎症反应的影响

• 发表时间: 2011
• 作者: 山口正昭;小林芳郎;永田喜三郎
• 通讯作者: 永田喜三郎

Regulation of the estrous cycle by opioid peptides from neutrophils infiltrated into female genital organ

渗入女性生殖器官的中性粒细胞阿片肽对动情周期的调节

• 发表时间: 2009
• 作者: Sohichiro S.;Nagata;K.;and Kobayashi Y.
• 通讯作者: and Kobayashi Y.

The mechanism underlying the appearance of late apoptotic neutrophils and subsequent TNF-α production at a late stage during Staphylococcus aureus bioparticle-induced peritoneal inflammation in inducible NO synthase-deficient mice

在金黄色葡萄球菌生物颗粒诱导的诱导型 NO 合酶缺陷小鼠腹膜炎症过程中，晚期凋亡中性粒细胞出现以及随后后期 TNF-α 产生的机制

• 发表时间: 2010
• 期刊: Biochemica et Biophysica Acta
• 作者: Shibata;T.;Nagata;K.;and Kobayashi;Y.
• 通讯作者: Y.