Myeloid regulatory cells in allergic airway inflammation

过敏性气道炎症中的骨髓调节细胞

• 批准号: 7753950
• 负责人: Jessy Satyadas Deshane
• 金额: $ 5.19万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7753950
• 关键词: Address; Adoptive Transfer; Air; Allergens; Allergic; Anti-Asthmatic Agents; Antigens; Asthma; Attenuated; Biological Availability; Bronchoalveolar Lavage Fluid; Cells; Chronic; Data; Disease; Equilibrium; Exhalation; Free Radicals; Generations; Immune; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Lung; Mediating; Mission; Modeling; Mus; Myelogenous; Myeloid Cells; NADPH Oxidase; National Heart, Lung, and Blood Institute; Neutrophil Infiltration; Nitric Oxide; Ovalbumin; Pathway interactions; Population; Process; Public Health; Recruitment Activity; Research Proposals; Role; Severity of illness; Source; Structure of parenchyma of lung; Superoxides; T-Cell Proliferation; Testing; Tissues; airway hyperresponsiveness; airway inflammation; allergic airway inflammation; antigen challenge; arginase; asthmatic patient; cytokine; human NOS2A protein; in vivo; mouse model; novel; research study

DESCRIPTION (provided by applicant): Hypothesis: Myeloid derived regulatory cells (MDRC), recruited to the lung during allergic airway inflammatory responses such as asthma, help to control the level of tissue inflammation by regulating the bioavailability of reactive free radicals, including nitric oxide (NO) and superoxide (02-). Specific Aims: (1) To test the hypothesis that myeloid subpopulations recruited to the lung of sensitized mice following antigen challenge generate and regulate the critical balance of reactive free radicals during allergic airway inflammation (2) Determine whether MDRC attenuate the asthmatic inflammatory response by mechanisms using reactive free radical species in a mouse model. Experimental Approach: C57BL/6, INOS-/- or B6 (Cg)-Ncf1m1 J/J mice will be sensitized intraperitoneally and challenged with the intranasal antigen, ovalbumin (OVA). Bronchoalveolar lavage (BAL) fluid and lung tissue will be examined for (1) dynamics of recruitment of MDRC (2) function of MDRC including phagocytic ability, and generation of cytokines and free radical species by MDRC. In addition, we will investigate (3) whether MDRC mediate suppression of T cell proliferation in vitro via iNOS, Arginase or NADPH oxidase pathways (4) whether MDRC mediate suppression of T cell proliferation following adoptive transfer in vivo and the role of NO and 02- in this effect, and (5) whether the adoptively transferred MDRC modulate airway hyper-responsiveness in a model of airway inflammation. Rationale: During allergic airway inflammatory responses, innate cells are recruited to the lung prior to adaptive immune cells. We present preliminary data to show (1) that two subsets of MDRC which generate O2- and NO are recruited to the lungs, and (2) MDRC suppress T cell proliferation via mechanisms that depend on free radicals, suggesting the potential for these cells to attenuate inflammation in vivo. Relevance to Public Health and the NHLBI Mission: The proposed studies will test directly the potential of MDRC to suppress asthma disease severity, potentially identifying novel targets for anti-asthmatic therapy.

描述（由申请人提供）：假设：髓样衍生的调节细胞（MDRC），在过敏性气道炎症反应中招募到肺部，例如哮喘，有助于通过调节反应性自由基的生物利用度（包括一氧化物氧化物（NO）和超级氧化物（NO）和超级氧化物（02-2），有助于控制组织炎症水平。具体目的：（1）检验以下假设：抗原挑战后，粒细胞亚群募集到敏化小鼠的肺中会产生并调节在过敏性气道炎症过程中反应性自由基的关键平衡（2）确定MDRC是否会通过使用反应自由的自由辐射物质中的机制来减轻MDRC的炎症反应。实验方法：C57BL/6，iNOS - / - 或B6（CG）-NCF1M1 J/J小鼠将腹膜内敏感，并用鼻内抗原，卵形蛋白（OVA）挑战。将检查支气管肺泡灌洗（BAL）液和肺组织（1）MDRC募集MDRC功能的动力学，包括吞噬能力，​​以及MDRC的细胞因子和自由基物种的产生。 In addition, we will investigate (3) whether MDRC mediate suppression of T cell proliferation in vitro via iNOS, Arginase or NADPH oxidase pathways (4) whether MDRC mediate suppression of T cell proliferation following adoptive transfer in vivo and the role of NO and 02- in this effect, and (5) whether the adoptively transferred MDRC modulate airway hyper-responsiveness in a model of airway inflammation.理由：在过敏性气道炎症反应中，先天细胞在适应性免疫细胞之前募集到肺部。我们提供了初步数据，以表明（1）将两个产生O2-和NO的MDRC子集募集到肺部，并且（2）MDRC通过依赖自由基的机制抑制T细胞增殖，这表明这些细胞在VIVO中减轻炎症的潜力。与公共卫生和NHLBI任务相关的是：拟议的研究将直接测试MDRC抑制哮喘疾病严重程度的潜力，并有可能识别抗心血症治疗的新靶标。