P CARINII PNEUMONIA--IMMUNOPATHOGENESIS OF LUNG INJURY

卡氏肺孢子虫在以下患者中产生危及生命的肺炎 免疫功能受损。尤其在患有以下疾病的患者中流行 艾滋病。虽然卡氏肺孢子虫肺炎(PCP)的特征是缺氧，但 卡氏肺孢子虫造成的肺损伤的类型和程度从未 明确的或具有特征的。该提案的目标是定义并开始 以确定PCP引起的肺部损害的特征。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 并在没有宿主免疫反应的情况下改变肺功能，即， 在SCID小鼠中；2)确定 宿主炎症反应参与了病理生理变化 发生在PCP中；以及3)确定对宿主的操纵 炎症反应可减轻脑梗塞的病理生理后遗症 五氯苯酚。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显著影响 PCP小鼠模型。使用最现代的分子/细胞和 生理学技术，包括评估患者的肺顺应性 这一提议将检验这样一种假设，即 卡氏肺囊虫肺炎的发病是卡氏肺孢子虫直接作用的结果。 对肺脏的影响及卡氏肺孢子虫驱动宿主炎症的影响 回应。这将通过仔细处理的各个方面来完成 通过炎症反应来确定对肺损伤的影响。如果这个 假设被证明是正确的，从建议中获得的信息 研究可以被用来开发新的治疗方式来改善 五氯联苯引起的发病率和死亡率。

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.