MONOCYTE INTEGRIN PROTEIN REGULATION BY M TUBERCULOSIS

描述：本课题拟研究细胞信号转导规律。 白细胞整合素分子。当前应用程序是从 意识到一大堆几乎被遗忘的关于结核杆菌影响的研究 在吞噬细胞上，可以追溯到1949年，现在可能是 基于更新的理解在分子水平上重新解释 整合素蛋白的存在和功能。去年， 候选人已经获得了大量的初步数据来支持 她的假设如下：(1)肉芽肿的关键方面 对结核分枝杆菌的应答由整合素分子介导；(2)毒力株 可能损害整合素的反应；以及(3)整合素的调节子 活化影响结核分枝杆菌感染的转归。具体目标 从假设出发：(1)研究信令机制和 单核细胞活化过程中整合素磷酸化的变化 聚集、MTB吞噬和多核巨细胞形成； (2)用单核细胞和肺泡巨噬细胞比较AIM 1的检测结果 来自患有或不患有艾滋病、患有或不患有艾滋病的男性和女性 结核病；(3)检测结核分枝杆菌或强毒菌株脂质的能力， Sulfolipid 1，抑制整合素功能；和(4)确定 不同免疫阶段个体的基础单核细胞功能 妥协，并测试信令的潜在增强效果 调节剂和整合素抗体。

DESCRIPTION: This proposes to study signal transduction regulation of leukocyte integrin molecules. The current application grew out of the realization that a body of mostly forgotten work about the effects of MTB on phagocytic cells, dating back as far as 1949, could now be reinterpreted at the molecular level based on more recent understanding of the existence and function of integrin proteins. In the last year, the candidate has acquired substantial preliminary data in support of her hypotheses as follows: (1) key aspects of the granulomatous response to MTB are mediated by integrin molecules; (2) virulent strains of MTB may impair integrin response; and (3) modulators of integrin activation influence the outcome of MTB infection. The specific aims follow from the hypotheses: (1) to study signalling mechanisms and integrin phosphorylation changes during activation of monocyte aggregation, MTB phagocytosis and multinucleated giant cell formation; (2) to compare results of Aim 1 using monocytes and alveolar macrophages from men and women with or without AIDS, and with or without tuberculosis; (3) to test the ability of MTB or a virulent strain lipid, sulfolipid 1, to inhibit integrin function; and (4) to determine baseline monocyte functions in individuals with various stages of immune compromise, and to test the potential enhancing effects of signalling regulators and integrin antibodies.