Role of Surfactant in Innate and Adaptive Immunity

表面活性剂在先天性和适应性免疫中的作用

• 批准号: 6758516
• 负责人: JO RAE WRIGHT
• 金额: $ 37.15万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6758516
• 关键词: allergens; antigen presentation; calcium flux; cell cell interaction; cytokine; dendritic cells; gene targeting; genetically modified animals; human tissue; immunity; inflammation; laboratory mouse; leukocyte activation /transformation; lung disorder; molecular pathology; opsonin; protein structure function; pulmonary surfactants; respiratory function; respiratory hypersensitivity; tissue /cell culture

DESCRIPTION (provided by applicant): Although pulmonary surfactant has been traditionally viewed as a surface tension reducing substance, recent studies demonstrate that it also functions in host defense. Two surfactant proteins, SP-A and SP-D, arc members of a family of innate immune proteins known as collectins that bind pathogens and facilitate the clearance by immune cells. SF-A and SP-D also regulate a variety of immune cell functions. The hypothesis to be tested in this proposal is that SP-A and SP-D interact with cells of both the adapative and innate immune systems to coordinately maximize defense against inhaled particles and pathogens while minimizing potentially harmful inflammatory consequences. We propose that SF-A and SP-D enhance uptake and presentation of antigens by dendritic cells, as they passes through the airspace in response to an inflammatory challenge, and that SF-A and SP-D suppress lymphocyte activation while they are in the alveolar and airway compartments, thereby minimizing damage to the delicate pulmonary epithelium that could occur in the lymphocytes were constantly activated in the airspaces. These effects would maximize the ability of dendritic cells to present antigen once they migrate to the lymph nodes and encounter lymphocytes that are no longer suppressed by SP-A or SP-D. This model is consistent with previous observations that lung lymphocytes are hyporesponsive compared to circulating lymphocytes and with our preliminary data showing that SP-A an SP-D inhibit lymphocyte proliferation and enhance antigen presentation by dendritic cells. The hypothesis will be tested by investigating 4 specific aims. Aim 1 is to determine if SP-A and SP-t enhance antigen uptake and presentation by dendritic cells. Aim 2 is to determine if SP-A and SP-D affect production of regulatory molecules (cytokines, cell surface receptors, and co-stimulatory molecules) b) dendritic cells stimulated with either antigen or LPS. Aim 3 is to investigate the mechanism by which SP-A and SP-D regulate lymphocyte activation. Aim 4 is to define the role of SP-A and SP-D in the pathogenesis o inflammatory lung disease in vivo using SF-A and SP-D deficient mice. These studies will provide information about the role of SF-A and SP-D in regulating the functions of two important cells of the adaptive about immune system and contribute to our understanding of the role of SF-A and SP-D inflammatory lung diseases.

描述（由申请人提供）：虽然肺表面活性剂已经