Cell Signaling of Host Defense

由迈克尔·B·费斯勒医学博士领导的国家环境卫生科学研究所内壁研究部呼吸生物学实验室的宿主防御小组自成立以来已进入第四个年头。我们现在已经发布了几份报告： 1.界定核受体肝脏X受体在调节肺天然免疫中的新作用的原创性出版物(Smoak K等人，《免疫学杂志》2008；180(5)：3305-12) 2.一项利用蛋白质组学的研究，发现了巨噬细胞对内毒素的反应中的新事件，脂多糖是一种环境先天性免疫刺激(Dhungana S等人，《摩尔细胞蛋白质组学》2009；8：201-13) 3.一份利用国家调查数据在美国人群中确定血清胆固醇和哮喘之间的新联系的报告(Fessler MB等人，J AllEnergy Clin Immunol 2009，正在出版中)。 4.2篇关于蛋白质组学方法学的综述文章(Dhungana S等人，方法Mol Biol2009a和2009b) 5.一篇关于Toll样受体在代谢综合征中的作用的综述文章(Fessler MB等人，Curr Opin Lipidol，2009年) 6.一篇关于中性粒细胞向肺内募集机制的综述文章(Cai等人，Am J Respir Cell Mol Biol，2009年出版)。 此外，另有一篇描述硬脂酰辅酶A去饱和酶在动脉粥样硬化中的新角色的合作论文正在修订中，《动脉硬化、血管生物学》和《血管生物学》最近又向《细胞代谢》(描述载脂蛋白AI在先天性免疫中的新角色)、《血液》(描述血脂异常对肺部宿主防御的影响)、《过敏》(描述了血清胆固醇与美国特应性疾病之间的新的流行病学关联)和《过敏与临床免疫学杂志》(描述了我们小组和NIEHS结构生物学实验室合作中的一种尘螨过敏原的结构)发表了另外4篇论文。 自上次报告以来，我们取得的其他成就包括：博士后团队成员David Draper博士和Jim Aloor博士获得2010年卓越研究院士奖，获得抽象旅行奖，并受邀在2009年美国胸科学会国际会议上向David Draper同事发表口头报告，小组成员凯瑟琳·斯莫克(生物学家)在2009年关于病原体受体的Keystone会议(加拿大班夫)上做口头陈述，由Fessler博士举办了5次区域研究研讨会，Fessler博士主持了一次科学研讨会，并在2009年美国胸腔学会国际会议上为海报会议提供了便利。此外，实验室还收集了5个活跃的研究项目的大量数据：1)载脂蛋白A-I和载脂蛋白E作为肺宿主防御调节因子的特征；2)胆固醇转运体Abcg1在肺宿主防御中的作用；以及3)经脂肪酸棕榈酸酯修饰的巨噬细胞蛋白的蛋白质组学鉴定。

The Host Defense Group of the Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, headed by Michael B. Fessler, MD now enters its fourth year at the NIEHS since inception. We have now published several reports: 1. an original publication that defines a novel role for the nuclear receptor Liver X Receptor in modulation of pulmonary innate immunity (Smoak K et al., Journal of Immunology 2008;180(5):3305-12) 2. an investigation using proteomics that has identified novel events in the response of the macrophage to lipopolysaccharide, an environmental innate immune stimulus (Dhungana S et al., Mol Cell Proteomics 2009; 8:201-13) 3. a report identifying a novel association between serum cholesterol and asthma in the U.S. population, using national survey data (Fessler MB et al., J Allergy Clin Immunol 2009, in press). 4. 2 review articles on proteomic methodology (Dhungana S et al., Methods Mol Biol 2009a and 2009b) 5. a review article on the role of Toll like Receptors in metabolic syndrome (Fessler MB et al., Curr Opin Lipidol 2009) 6. a review article on mechanisms of neutrophil recruitment to the lung (Cai et al., Am J Respir Cell Mol Biol 2009, in press). In addition, one additional collaborative paper that describes a novel role for stearoyl-CoA desaturase in atherosclerosis is under revision for Arteriosclerosis, Thombosis, and Vascular Biology, and 4 additional manuscripts have recently been submitted to the journals Cell Metabolism (describes a novel role for apolipoprotein AI in innate immunity), Blood (describes effect of dyslipidemia on pulmonary host defense), Allergy (describes a new epidemiologic association between serum cholesterol and atopy in the U.S. population), and Journal of Allergy and Clinical Immunology (describes the structure of a dust mite allergen in a collaboration between our Group and the NIEHS Laboratory of Structural Biology). Additional accomplishments since our last report include receipt of a 2010 Fellow Award for Research Excellence by postdoctoral fellow Group members David Draper, Ph.D. and Jim Aloor, Ph.D., receipt of an abstract travel award as well as invitation to deliver an oral presentation to fellow David Draper at the 2009 American Thoracic Society International Conference, delivery by Group member Kathleen Smoak (biologist) of an oral presentation at the 2009 Keystone Conference on Pathogen Receptors (Banff, Canada), delivery of 5 regional research seminars by Dr. Fessler, and Chairing by Dr. Fessler of a Scientific Symposium as well as Facilitation of a poster session at the 2009 American Thoracic Society International Conference. In addition, substantial data has been collected on 5 active research projects in the laboratory: 1) characterization of apoplipoprotein A-I and apolipoprotein E as regulators of pulmonary host defense; 2) characterization of the role of the cholesterol transporter ABCG1 in pulmonary host defense; and 3) proteomic identification of macrophage proteins that are modified with the fatty acid palmitate.