P CARINII PNEUMONIA--IMMUNOPATHOGENESIS OF LUNG INJURY

卡氏肺孢子虫会在以下患者中产生危及生命的肺炎： 免疫力低下它在患有以下疾病的患者中尤其普遍： 艾滋病虽然卡氏肺孢子虫肺炎（PCP）的标志是缺氧， 卡氏肺吸虫引起的肺损伤的类型和程度从未被 定义或特征。本提案的目标是定义并开始 来描述五氯苯酚造成的肺损伤 这将是 通过完成以下具体目标来实现：1）确定 卡氏肺孢子虫直接造成伤害的程度和方式 以及在缺乏宿主免疫应答的情况下改变的肺功能，即， 在SCID小鼠中; 2）确定 宿主炎症反应导致病理生理变化 发生在PCP;和3）以确定是否操纵主机 炎症反应可以改善 五氯酚初步实验表明宿主的炎症反应 其本身对SCID患者的整体肺损伤有重要作用 PCP小鼠模型。 使用最现代的分子/细胞和 生理技术，包括评估肺顺应性， 通风的活老鼠，这项建议将测试的假设， PCP的发病机制是卡氏肺孢子虫直接作用和 以及卡氏肺孢子虫驱动的宿主炎症反应的影响 反应这将通过仔细操纵 炎症反应，以确定对肺损伤的影响。如果这 假设被证明是正确的，从提出的信息 研究可用于开发新的治疗方式，以改善 五氯苯酚导致的发病率和死亡率。

Pneumocystis carinii produces a life-threatening pneumonia in patients who are immunocompromised. It is especially prevalent among patients with AIDS. While the hallmark of P. carinii pneumonia (PCP) is hypoxia, the type and extent of lung injury produced by P. carinii has never been defined or characterized. The goal of this proposal is to define and begin to characterize the pulmonary insult resulting from PCP. This will be accomplished by completing the following specific aims: 1) to determine the extent and means by which P. carinii directly contributes to injury and altered lung function in the absence of a host immune response, i.e., in a SCID mouse; 2) to determine the extent and mechanism by which the host inflammatory response contributes to the pathophysiological changes that occur in PCP; and 3) to determine whether manipulation of the host inflammatory response can ameliorate the pathophysiological sequelae of PCP. Preliminary experiments show that the host inflammatory response itself contributes significantly to the overall pulmonary injury in a SCID mouse model of PCP. Using the most modem molecular/cellular and physiologic techniques, including assessment of lung compliance in a ventilated living mouse, this proposal will test the hypothesis that the pathogenesis of PCP is the result of both the direct effect of P. carinii on the lung and the effect of the P. carinii-driven host inflammatory response. This will be done by carefully manipulating various aspects of the inflammatory response to determine the effect on lung injury. If this hypothesis is proven correct, the information gained from the proposed studies can be utilized to develop new therapeutic modalities to improve the morbidity and mortality resulting from PCP.