MONOCYTE INTEGRIN PROTEIN REGULATION BY M TUBERCULOSIS

描述：本研究旨在研究细胞信号转导调控， 白细胞整合素分子。 当前的应用程序源于 意识到一个关于MTB影响的大多被遗忘的工作机构 早在1949年， 根据最近的理解，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， 她的假设如下：（1）肉芽肿的关键方面 对MTB的应答由整合素分子介导;（2）强毒株 MTB的可能损害整合素反应;和（3）整合素的调节剂 活化影响MTB感染的结果。 具体目标 根据假设：（1）研究信号机制， 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)比较Aim 1使用单核细胞和肺泡巨噬细胞的结果 有没有艾滋病，有没有 （3）检测MTB或强毒株脂质体的能力， 硫脂质1，以抑制整联蛋白功能;和（4）确定 不同免疫阶段个体的基线单核细胞功能 妥协，并测试信号的潜在增强效果 调节剂和整联蛋白抗体。

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.