What is the function of integrin allb in mast cell?

肥大细胞中整合素 allb 的功能是什么？

• 批准号: 17390287
• 负责人: KITAURA Jiro
• 金额: $ 10.51万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390287/
• 关键词: integrin; mast cell; fibrinogen; Integrinα IIbβ3; マスト胞; 接着; フイブリノーゲン; Integrinαvβ3; フォンビルブランドファクター; ビトロネクチン; 炎症増悪・修復; Integrin αIIbβ3; Integrin αvβ3; IntegrinαIIbβ3; ファイブリンーゲン; IntegrinαVβ3

Integrin αIIb, a well-known marker of megakaryocyte-platelet lineage, has been recently recognized on hemopoietic progenitors. We now demonstrate that integrin αIIb is highly expressed on mouse and human mast cells including mouse bone marrow-derived mast cells, peritoneal mast cells, and human cord blood-derived mast cells, and that its binding to extracellular matrix proteins leads to enhancement of biological functions of mast cells in concert with various stimuli. With exposure to various stimuli, including cross-linking of FcεRI and stem cell factor, mast cells adhered to extracellular matrix proteins such as fibrinogen and von Willebrand factor in an integrin αIIb-dependent manner. In addition, the binding of mast cells to fibrinogen enhanced proliferation, cytokine production, and migration and induced uptake of soluble fibrinogen in response to stem cell factor stimulation, implicating integrin αIIb in a variety of mast cell functions. In conclusion, mouse and human mast cells express functional integrin αIIb.Analysis of integrin αIIb-deficient mouse delineated that integrin αIIb competed with integrin αV in associating with integrin β3 in mast cells and that mast cells-associated allergic responses were attenuated by integrin αIIb deficiency. In addition, the number of mast cells in the skin of the back, but not ear, was decreased in integrin αIIb-deficient mouse as compared with wild type mouse. Collectively, integrin αIIbβ3 might be involved in the distribution and function of mast cells, although the effect of enhanced expression levels of integrin αVβ3 in the absence of integrin αIIb must be considered. Further examination is necessary to completely understand the in vivo function of integrin αIIb, leading to new therapeutic approaches forthcoming for mast cell-mediated diseases.

整合素αIIb是巨核细胞-血小板谱系的标志物，近年来被发现存在于造血祖细胞上。我们现在证明，整合素αIIb在小鼠和人肥大细胞（包括小鼠骨髓来源的肥大细胞、腹膜肥大细胞和人脐带血来源的肥大细胞）上高度表达，并且其与细胞外基质蛋白的结合导致肥大细胞与各种刺激相一致的生物学功能增强。当暴露于各种刺激（包括FcεRI和干细胞因子的交联）时，肥大细胞以整合素α IIb依赖的方式粘附于细胞外基质蛋白（如纤维蛋白原和von Willebrand因子）。此外，肥大细胞与纤维蛋白原的结合增强了增殖、细胞因子产生和迁移，并诱导可溶性纤维蛋白原对干细胞因子刺激的摄取，这表明整合素αIIb参与了多种肥大细胞功能。结论：小鼠和人肥大细胞表达功能性整合素αIIb，整合素α IIb缺陷小鼠的分析表明，整合素αIIb与整合素αV竞争结合肥大细胞中的整合素β3，并且整合素αIIb缺陷减弱肥大细胞相关的过敏反应。此外，与野生型小鼠相比，整合素α IIb缺陷型小鼠背部皮肤中的肥大细胞数量减少，但耳部皮肤中的肥大细胞数量没有减少。总的来说，整合素αIIbβ3可能参与肥大细胞的分布和功能，尽管必须考虑在缺乏整合素αIIb的情况下整合素αVβ3表达水平增强的影响。进一步的检查是必要的，以完全了解整合素αIIb在体内的功能，导致肥大细胞介导的疾病的新的治疗方法即将到来。

项目成果

Mast cell survival and activation by IgE in the absence of antigen: aconsideration of the biologic mechanisms and relevance.

在没有抗原的情况下，肥大细胞存活并被 IgE 激活：考虑生物学机制和相关性。

• 发表时间: 2005
• 期刊: J. Immunol. 175
• 作者: 塚本博丈;西村泰治;山西 吉典;渡辺(大河内) 直子;山西 吉典;川島 敏行;北浦 次郎;伊沢 久未;Hong H;伊沢 久未;呂 洋;沖 俊彦;沖 俊彦;中島 秀明;中島 秀明;福地 由美;川島 敏行;沖俊彦;中島秀明;北浦 次郎;北浦 次郎;川上 敏明
• 通讯作者: 川上 敏明

IgE- and IgE+Ag-mediated migration of mast cells in an autocrine/paracrine fashion

IgE 和 IgE Ag 介导的肥大细胞以自分泌/旁分泌方式迁移

• 发表时间: 2005
• 作者: Kitaura;J;et. al.
• 通讯作者: et. al.

Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinases

• DOI: 10.4049/jimmunol.174.8.4495
• 发表时间: 2005-04-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Kitaura, J;Eto, K;Kawakami, T
• 通讯作者: Kawakami, T

Integrin αIIbβ3 induces the adhesion and activation of mast cells through interaction with fibrinogen

整合素αIIbβ3通过与纤维蛋白原相互作用诱导肥大细胞粘附和活化

• 发表时间: 2006
• 期刊: J.Immunol. 176
• 作者: Baba T;Mimura J;Nakamura N;Harada N;Yamamoto M;Morohashi K;Fujii-Kuriyama Y.;沖 俊彦;中島 秀明;中島 秀明;福地 由美;川島 敏行;沖俊彦
• 通讯作者: 沖俊彦

AML1 mutations induced MDS and MDS/AML in a mouse BMT model

• DOI: 10.1182/blood-2007-01-068346
• 发表时间: 2008-04-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Watanabe-Okochi, Naoko;Kitaura, Jiro;Kitamura, Toshio
• 通讯作者: Kitamura, Toshio