CATECHOLAMINE REGULATION OF MACROPHAGE FUNCTION

描述(改编自申请人摘要)：感染人类 免疫缺陷病毒导致全身性免疫抑制，导致 增加了宿主对感染的易感性。感染 由机会性病原体引起的发病率和死亡率 与艾滋病有关。分枝杆菌疾病的发病率，包括 由结核分枝杆菌和禽类引起的感染有所增加 在艾滋病毒感染者中显著增加。在美国的研究 研究人员的实验室在MHC II类中存在相关差异 在小鼠体内表达对分枝杆菌生长具有抵抗力的基因。类似 人类单核细胞表达MHC II类分子的差异 调查人员也确认了这一点。压力可能是一个重要的 与分枝杆菌疾病易感性有关的辅因子，而这个实验室 表明束缚压力会导致Ia的抑制 表情。Ia表达的差异表明可能存在 小鼠巨噬细胞激活水平的差异 对分枝杆菌的生长具有抵抗力或易感性。目的 这份续签申请将确定压力在 分枝杆菌感染发病机制的调控及其相关性 这些差异表现为Ia表达的变化。因此，约束压力 可能会通过允许机会主义的 病原体在单核吞噬细胞内形成并生长。 具体目标是：(1)确定约束对经济增长的影响 分枝杆菌在体内的生长；(2)确定束缚应激是否 分枝杆菌生长的诱导改变是由 下丘脑-垂体-肾上腺轴；(3)确定 交感神经系统在束缚应激介导的脑损伤中的作用 分枝杆菌生长；(4)测定束缚应激对小鼠的影响 巨噬细胞的体外活性；(5)确定其作用机制 束缚应激介导巨噬细胞功能的改变。

DESCRIPTION (Adapted form Applicant's Abstract):Infection with the human immunodeficiency virus leads to a systemic immunosuppression that results in an increase in the susceptibility of the host to infection. Infection by opportunistic pathogens is responsible for the morbidity and mortality associated with AIDS. The incidence of mycobacterial diseases, including infections caused by M tuberculosis and avium, has increased significantly among HIV-infected individuals. Studies in the investigator's laboratory have correlated differences in MHC class II expression with resistance to mycobacterial growth in mice. Similar differences in MHC class II expression by human monocytes have been identified also by the investigators. Stress may be an important cofactor in susceptibility to mycobacterial disease, and this laboratory has shown that restraint stress results in a suppression of Ia expression. Differences in Ia expression indicate that there may be differences in the level of activation of the macrophages in mice that are resistant or susceptible to mycobacterial growth. The purpose of this renewal application will be to determine the role of stress in modulating the pathogenesis of mycobacterial infection and to correlate these differences to changes in Ia expression. Thus, restraint stress may alter the host parasite relationship by allowing the opportunistic pathogen to become established and grown within mononuclear phagocytes. The specific aims are: (1) to determine the effect of restraint on the growth of Mycobacteria in vivo; (2) to determine whether restraint stress induced alteration in mycobacterial growth is mediated by the hypothalamic-pituitary-adrenal axis; (3) to determine the role of the sympathetic nervous system in restraint stress mediated alteration in mycobacterial growth; (4) to determine the effect of restraint stress on the in vitro activity of macrophages; and (5) to determine the mechanism of restraint stress mediated alteration in macrophage function.