AIDS ASSOCIATED PLEURAL INFECTION

艾滋病患者继续主要死于呼吸道感染。细菌性脓胸是艾滋病患者肺炎的常见并发症。虽然多种微生物可引起艾滋病患者的胸膜感染，但引起脓胸的最常见微生物之一是金黄色葡萄球菌。这是该建议的假设，募集的中性粒细胞代表参与细菌性脓胸中有效的胸膜抗菌宿主防御的重要吞噬细胞。我们在CD 4基因敲除小鼠中建立了一种细菌性脓胸模型，该模型模拟了艾滋病患者的细菌性脓胸。胸膜间皮细胞通过产生中性粒细胞活化和趋化性趋化因子MIP-2在中性粒细胞募集中起关键作用，并且在我们的葡萄球菌性脓胸小鼠模型中，KC通过抑制体内区室化趋化因子的产生来改变胸膜中性粒细胞募集和细菌清除。巨噬细胞炎性蛋白-2（MIP-2）和KC（鼠Gro-alpha）。CD 4耗竭的抑制作用部分是由于Th 1型干扰素γ（IFN-γ）和Th 2型细胞因子白细胞介素-10（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。使用在体内模型的葡萄球菌脓胸在CD 4，敲除小鼠，我们将评估的调节MIP-2和KC的第一次和第二次细胞因子。在体外，间皮细胞对S.金黄色葡萄球菌通过释放中性粒细胞趋化因子及其调控进行研究。了解调节中性粒细胞募集到胸膜腔的机制可能有助于我们辨别艾滋病患者暴发性细菌性脓胸的病理生理学，并可能有助于开发增强宿主防御反应的治疗方法。

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.