Tetraspanins in Asthma and Eosinophilic Lung Disease

四跨膜蛋白在哮喘和嗜酸性肺病中的作用

• 批准号: 7940983
• 负责人: Praveen Akuthota
• 金额: $ 5.99万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-07-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7940983
• 关键词: Affect; Allergic inflammation; American; Antigen Presentation; Antigen-Presenting Cells; Antigens; Asthma; B-Lymphocytes; Blast Cell; CD81 gene; Cell membrane; Cell physiology; Cell surface; Cells; Cellular biology; Characteristics; Complex; Cytoplasmic Granules; Data; Dendritic Cells; Disease; Effector Cell; Flow Cytometry; Grant; HLA-DR Antigens; Histocompatibility Antigens Class II; Human; Immunofluorescence Microscopy; Inflammation; Inflammatory; Integral Membrane Protein; KAI1 gene; Laboratories; Lipids; Literature; Lung; Lung diseases; Mediating; Membrane; Membrane Microdomains; Membrane Proteins; Microscopy; Parasitic Diseases; Parasitic infection; Peptides; Process; Proteins; Regulation; Research; Role; Signal Transduction; Staging; Surface; Surface Antigens; T-Lymphocyte; Techniques; Western Blotting; Work; airway inflammation; allergic airway disease; cytotoxic; density; eosinophil; experience; human PHEMX protein; insight; interest; member; monocyte; protein complex; response

DESCRIPTION (provided by applicant): Eosinophils have long been thought to function exclusively as "end stage effector" cells in asthma and other eosinophilic lung disorders, acting through the release of cytotoxic substances. However, mounting evidence has demonstrated that eosinophils have important immunoregulatory roles in mediating airways inflammation. One such well-established key immunoregulatory role is their function as anitgen-presenting cells (APCs). The purpose of this grant is to explore the organization of the antigen presentation machinery on the surface membrane of human eosinophils. Specifically, the involvement of tetraspanin molecules and lipid rafts may be important in allowing eosinophils to function as professional APCs. The specific aims of the research proposed will investigate the following hypotheses: 1) the tetraspanin CD9 is associatedwith antigen-presentation machinery in human eosinophils, 2) MHC Class II Is located predominantly in lipid rafts on the cell surface of human eosinophils, 3) CD9 associates with MHC Class II in lipid rafts of human eosinophils, and 4) other non-CD9 tetraspanins associate with MHC Class II in intracellular compartments in human eosinophils. The proposed research will utilize co-immunopreciptation, lipid raft isolation, immunofluoresecence microscopy, flow cytometry, and Western blot in order to establish the involvement of tetraspanins and lipid rafts in the antigen presentation complex of human eosinophils. Establishment of the association between antigen presentation proteins, tetraspanins, and lipid rafts would further establish eosinophils as unique antigen presenation cells with a likely pivotal immunoregulatory role in the perpetuation of asthma. Asthma is a common disorder that affects millions of Americans, but a complete understanding of the disease remains elusive. Eosinophils are inflammatory cells that have been noted to be associated with asthma and other lung diseases. Our research aims to better understand how eosinophils organize their surface proteins with the hope that this will provide insight into their true role in asthma.

描述（由申请人提供）：长期以来，嗜酸性粒细胞一直被认为在哮喘和其他嗜酸性肺部疾病中专门充当“末期效应”细胞，通过释放细胞毒性物质发挥作用。然而，越来越多的证据表明，嗜酸性粒细胞在介导气道炎症方面具有重要的免疫调节作用。其中一项公认的关键免疫调节作用是它们作为抗原呈递细胞 (APC) 的功能。该资助的目的是探索人类嗜酸性粒细胞表面膜上抗原呈递机制的组织。具体来说，四跨膜蛋白分子和脂筏的参与对于嗜酸性粒细胞发挥专业 APC 的功能可能很重要。该研究的具体目标将调查以下假设：1) 四跨膜蛋白 CD9 与人类嗜酸性粒细胞中的抗原呈递机制相关，2) MHC II 类主要位于人类嗜酸性粒细胞表面的脂筏中，3) CD9与人嗜酸性粒细胞脂筏中的 MHC II 类相关，4) 其他非 CD9 四跨膜蛋白与 MHC II 类相关在人嗜酸性粒细胞的细胞内区室中。拟议的研究将利用免疫共沉淀、脂筏分离、免疫荧光显微镜、流式细胞术和蛋白质印迹来确定四跨膜蛋白和脂筏在人嗜酸性粒细胞抗原呈递复合物中的参与。抗原呈递蛋白、四跨膜蛋白和脂筏之间关联的建立将进一步确立嗜酸性粒细胞作为独特的抗原呈递细胞，在哮喘的持续存在中可能具有关键的免疫调节作用。哮喘是一种影响数百万美国人的常见疾病，但对这种疾病的全面了解仍然难以捉摸。嗜酸性粒细胞是一种炎症细胞，已被认为与哮喘和其他肺部疾病有关。我们的研究旨在更好地了解嗜酸性粒细胞如何组织其表面蛋白，希望这能深入了解它们在哮喘中的真正作用。