INTERACTIONS OF BACTERIAL LPS WITH EPIDERMAL DENDRITIC CELLS

细菌脂多糖与表皮树突细胞的相互作用

• 批准号: 6235775
• 负责人: RICHARD L. KITCHENS
• 金额: $ 5.04万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-10 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6235775
• 关键词: CD antigens; Langerhans' cell; acylation; animal tissue; antigen presentation; bacterial proteins; confocal scanning microscopy; dendritic cells; laboratory mouse; lipopolysaccharides; membrane proteins; protein degradation; receptor binding

The objective of this project is to understand the molecular mechanisms by which murine Langerhans cells (LC) respond to bacterial lipopolysaccharide (LPS), an environmentally ubiquitous and medically important bacterial molecule. The hypothesis to be tested is that LC have specific and sensitive mechanisms for binding, internalizing, and catabolizing LPS. The best characterized candidate receptor in the recognition-response system for lipopolysaccharide is CD14, a glycosylphosphatidylinositol-anchored protein on the surfaces of monocytes, macrophages, and neutrophils. Relevant preliminary data describe extensive experience by the investigators with LPS interactions with neutrophils and monocyte-macrophage, and many of these techniques will be used to study LPS-LC interactions. Recent studies in collaboration with Dr. Akira Takashima demonstrate that LPS has the capacity to modulate the immune function of an epidermal LC line (Dendritic Cell lin x552). Upon stimulation with LPS, x552 cells begin to exhibit mature features, including; a) elevated expression of MHC class II, CD80 and CD86, b) secretion of relatively large amount of IL-1-beta, IL-6, and TNF-alpha, and c) potent capacity to activate naive T cells in vitro as well as in vivo. Specific aims are: 1) To characterize the binding receptor(s) for LPS on LC. 2) To analyze the internalization and catabolism (deacylation) of LPS by LC. 3) To study the ability of lipid A partial structure to mimic or block LPS actions on LC. It is possible that related analogs of LPS could be useful clinically for modulating LC responses to cutaneous antigens. In addition, monophosphoryl lipid A is in clinical trails as an immunomodulator to prevent post-operative infections; understanding its interactions with LC might thus have clinical relevance in the near future.

该项目的目的是了解分子 鼠Langerhans细胞（LC）响应的机制 细菌脂多糖（LPS），一种环境无处不在的 和具有医学重要的细菌分子。 假设是 测试的是LC具有特定和敏感的机制 结合，内在化和分解代谢LP。 最好的 在识别反应中的特征候选受体 脂多糖的系统是CD14，A 糖基磷脂酰肌醇锚定蛋白在表面的表面 单核细胞，巨噬细胞和中性粒细胞。 相关的初步 数据描述了调查员有LP的丰富经验 与中性粒细胞和单核细胞巨噬细胞的相互作用，许多 这些技术将用于研究LPS-LC相互作用。 最近与Akira Takashima博士合作的研究 证明LPS具有调节免疫的能力 表皮LC系的功能（树突状细胞Lin X552）。 之上 LPS刺激，X552细胞开始表现出成熟的特征， 包括; a）MHC II类，CD80和 CD86，b）分泌相对较大的IL-1-β，IL-6， 和tnf-alpha，以及c）激活幼稚T细胞的能力 体外和体内。 具体目的是：1）表征 LC上LPS的结合受体。 2）分析 LC对LPS的内在化和分解代谢（脱氧）。 3）到 研究脂质的部分结构与模仿或块LPS的能力 在LC上的动作。 LP的相关类似物可能是 临床上有用可调节LC对皮肤的反应 抗原。 此外，单磷酸脂质A在临床踪迹中 作为预防术后感染的免疫调节剂； 因此，了解其与LC的相互作用可能有临床 相关性在不久的将来。