AIDS ASSOCIATED PLEURAL INFECTION

艾滋病相关胸膜感染

• 批准号: 6603127
• 负责人: Veena B. Antony
• 金额: $ 1.04万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-15 至 2003-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6603127
• 关键词: AIDS; Staphylococcus aureus; cell migration; chemokine; enzyme linked immunosorbent assay; genetically modified animals; helper T lymphocyte; interferon gamma; interleukin 10; interleukin 4; laboratory mouse; neutralizing antibody; neutrophil; opportunistic infections; passive immunization; respiratory infections

Patients with AIDS continue to die predominantly as a result of respiratory infections. Bacterial empyema with pyogenic organisms is a common complication of pneumonia in patients with AIDS. Though multiple organisms can cause pleural infections in patients with AIDS, one of the commonest organisms to cause empyema is Staphylococcus aureus. It is the hypothesis of this proposal that recruited neutrophils represent important phagocytic cells involved in effective pleural antibacterial host defense in bacterial empyema. We have developed a model of bacterial empyema in CD4 knockout mice that mimics bacterial empyema in patients with AIDS. Pleural mesothelial cells play a critical role in neutrophil recruitment by the production of neutrophil activating and chemotactic chemokines MIP-2, and KC in our murine model of staphylococcal empyema CD4 depletion alters pleural neutrophil recruitment and bacterial clearance by inhibition the in vivo compartmentalized production of the chemokines. Macrophage inflammatory protein-2 (MIP-2) and KC (murine gro-alpha). The inhibitory effect of CD4 depletion is in part due to the relative imbalance between Th1 type Interferon Gamma (IFN-gamma) and Th2 type cytokines, Interleukin-10 (IL-10). We will evaluate our hypothesis both in vivo and in vitro. Using an in vivo model of staphylococcal empyema in CD4, knockout mice, we will evaluate the regulation of MIP-2 and KC by 1TH and 2TH cytokines. In vitro, mesothelial cell responses to S. Aureus by release of neutrophil chemokines and their regulation will be studied. Understanding the mechanism of regulation of neutrophil recruitment to the pleural space may help us discern the pathophysiology of the fulminant bacterial empyema seen in patients with AIDS and may help develop therapeutic modalities that augment host defense responses.

由于呼吸道感染，患有艾滋病的患者继续死亡。伴有化脓性生物的细菌脓肿是艾滋病患者的肺炎常见并发症。尽管多种生物可能会引起艾滋病患者的胸膜感染，但引起脓胸的最常见生物之一是金黄色葡萄球菌。这一提议的假设是，招募的中性粒细胞代表了与细菌毛细血管中有效的胸膜抗菌宿主防御有关的重要吞噬细胞。我们已经在CD4基因敲除小鼠中开发了一种细菌性脓肿的模型，该模型在艾滋病患者中模仿细菌嗜酸症。胸膜间皮细胞通过产生嗜中性粒细胞激活和趋化性趋化因子MIP-2和KC在我们的葡萄球菌脓肿的鼠模型中，在葡萄球菌脓肿CD4耗竭的鼠类中性中性膜中性膜和细菌清除率通过抑制构成促成促成促进性化的化学因素来改变胸膜中性脱脂和细菌清除，从而改变了中性粒细胞的中性粒细胞在中性粒细胞募集中的关键作用。巨噬细胞炎症蛋白2（MIP-2）和KC（鼠粒α）。 CD4耗竭的抑制作用部分是由于Th1型干扰素伽马（IFN-GAMMA）和Th2型细胞因子（Iltleukin-100（IL-10）之间的相对失衡）。我们将在体内和体外评估我们的假设。使用CD4中敲除小鼠的葡萄球菌富裕症的体内模型，我们将通过第1和第2个细胞因子评估MIP-2和KC的调节。在体外，将研究中性粒细胞趋化因子及其调节对金黄色葡萄球菌对金黄色葡萄球菌的反应。了解中性粒细胞募集到胸膜空间的机制可能有助于我们辨别出在患有艾滋病患者中可见的暴发细菌性脓肿的病理生理学，并可能有助于发展治疗方式，以增强宿主防御反应。