P CARINII PNEUMONIA INDUCES LUNG FIBRIN(OGEN) EXPRESSION

描述：（改编自申请人摘要）。该提案将测试 凝血因子过量产生的假说 纤维蛋白原（FBG）和纤维蛋白[下文称为纤维蛋白（原）]， PCP期间的肺可能会加重损害， 疾病 这项研究的长期目标是阐明 参与炎症过程的分子机制， 宿主反应期间FBG基因表达和纤维蛋白（原）产生 变成了五氯酚具体目标是：1.为了阐明导致 在PCP过程中，使用一种新的方法增加肺中FBG基因（Aa/BB/g）的表达， PCP的雪貂模型（a、B、d部分）和SCID小鼠模型（c部分）。 这一目标将包括评估以下方面： FBG A α、B β和γ mRNA的不协调表达; FBG和IL-6 mRNA表达与PCP进展（雪貂模型） 和PCP的分辨率（SCID小鼠模型）;和诱导肺特异性 FBG基因表达与全身炎症 2.探讨 肺中FBG基因表达的分子机制[雪貂模型 和A549支气管肺泡细胞培养物BEC）]，重点关注 FBG基因的转录速率。3.以确定是否 肺中FBG mRNA表达升高导致 完整FBG蛋白在体内（通过免疫电子显微镜）和在原发性 BEC和A549细胞。4.评估肺的功能意义 上皮细胞来源的FBG。研究人员认为， FBG基因表达和纤维蛋白（原）产生的机制， 在与PCP相关的炎症反应期间，肺组织将 提供了一个更广泛的理解纤维蛋白（原）的作用， 体内平衡和止血，并可能导致改善 PCP和其他肺部炎症性疾病的管理。

DESCRIPTION: (Adapted from Applicant's Abstract). This proposal will test the hypothesis that excessive production of blood coagulation factor fibrinogen (FBG) and fibrin [henceforth referred to as fibrin(ogen)] in the lung during PCP may exacerbate damage and result in aggravated lung disease. The long range goal of the research is to elucidate the molecular mechanisms involved in inflammatory processes that modulate FBG gene expression and fibrin(ogen) production during the host response to PCP. The specific aims are: 1. To elucidate the events leading to increased FBG gene (Aa/BB/g) expression in lung during PCP using a ferret model of PCP (sections a,b,d) and a SCID mouse model (section c). This aim will include assessment of the following: coordinate versus dyscoordinate expression of the FBG Aalpha, BBeta and gamma mRNAs; expression of FBG and IL-6 mRNA with progression of PCP (ferret model) and resolution of PCP (SCID mouse model); and induction of lung specific FBG gene expression with systemic inflammation. 2. To investigate the molecular mechanisms of FBG gene expression in the lung [ferret model and A549 bronchoalveolar cell cultures BEC)] focusing on the transcriptional rate of the FBG gene. 3. To determine whether the elevated expression of FBG mRNAs in lung results in translation of intact FBG protein in vivo (by immunoelectron microscopy) and in primary BEC and A549 cells. 4. To assess the functional significance of lung epithelial cell-derived FBG. The investigator believes that the study of the mechanisms of FBG gene expression and fibrin(ogen) production in lung tissue during an inflammatory response associated with PCP will provide a broader understanding of the role of fibrin(ogen) in both homeostasis and hemostasis, and may lead to improvements in the management of PCP and other lung inflammatory diseases.