P CARINII PNEUMONIA INDUCES LUNG FIBRIN(OGEN) EXPRESSION

描述：(改编自申请人摘要)。这项提议将检验 凝血因子过度产生的假说 纤维蛋白原(Fbg)和纤维蛋白[以下简称纤维蛋白(Ogen)] PCP过程中的肺可能会加重损伤并导致加重的肺 疾病。这项研究的长期目标是阐明 参与调节炎症过程的分子机制 寄主反应过程中纤维蛋白原基因的表达和纤维蛋白原的产生 致PCP。具体目标是：1.澄清导致 阿司匹林促进PCP肺组织纤维蛋白原基因(AA/BB/g)的表达 PCP雪貂模型(a、b、d节)和SCID小鼠模型(c节)。 这一目标将包括以下评估：协调与 Fbgα、BBeta和Gamma mRNAs表达失调； FBG和IL-6mRNA在PCP进展过程中的表达(雪貂模型) 和PCP(SCID小鼠模型)的分辨；以及诱导肺特异性 Fbg基因表达与全身炎症的关系。2.调查 Fbg基因在肺组织中表达的分子机制 和A549支气管肺泡细胞培养)]专注于 Fbg基因的转录速率。3.确定是否 Fbg mRNAs在肺组织中的表达升高导致 体内(免疫电子显微镜)和原代培养的完整FBG蛋白 BEC和A549细胞。4.评价肺的功能意义 上皮细胞来源的FBG。调查人员认为，这项研究 Fbg基因表达和纤维蛋白原产生机制的研究进展 与PCP相关的炎症反应期间的肺组织将 提供对纤维蛋白(原)在这两种疾病中作用的更广泛的理解 动态平衡和止血，并可能导致改善 肺囊性肺炎和其他肺部炎症性疾病的处理。

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.