SUBSTANCE P AND THE PATHOGENESIS OF CRYPTOSPORIDIOSIS IN AIDS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：隐孢子虫感染会导致艾滋病患者出现危及生命的腹泻。隐孢子虫病的发病机制是肠道生理性改变。我们建立了由SIV感染的猕猴空肠组织感染微小隐孢子虫的体外模型，并研究了P物质(SP)在隐孢子虫病发病机制中的作用。 方法：在体外隐孢子虫感染模型中，用双抗体夹心法检测空肠SP基因和蛋白的表达，用Ussing小室技术检测其电生理改变。用免疫组织化学和荧光去卷积显微镜研究了SIV感染猕猴和未感染自然发生隐孢子虫病的猕猴空肠中SP的表达。 结果：体外隐孢子虫感染组织和自然发生隐孢子虫病SIV感染猕猴的组织中SP蛋白水平高于SIV感染动物组织和无隐孢子虫病证据的SIV感染动物组织。在我们的隐孢子虫感染的体外模型中，我们展示了被SP受体拮抗剂治疗所阻断的病理生理改变。 结论：SP受体拮抗剂可用于治疗艾滋病相关的隐孢子虫病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Back ground: Cryptosporidium infection leads to life threatening diarrhea in AIDS patients. Pathogenesis of cryptosporidiosis is due to intestinal physiological alterations. We devised an ex-vivo model using ex-vivo C. parvum infection of jejunal tissues derived from SIV infected macaques and studied the role of substance P (SP) in the pathogenesis of cryptosporidiosis. Methods: We measured jejunal SP mRNA and protein levels using ELISA , and electrophysiological alterations using the Ussing chamber technique in an ex-vivo model of Cryptosporidium infection. Paraformaldehyde fixed jejunum from SIV infected macaques with and without naturally-occurring cryptosporidiosis was studied for SP expression by immunohistochemistry and fluorescence deconvolution microscopy. Results: Ex-vivo Cryptosporidium infected tissues and tissues from SIV infected macaques with naturally-occurring cryptosporidiosis demonstrated elevated SP protein levels compared to tissues from SIV-infected animals without ex-vivo C. parvum infection or tissues from SIV-infected animals that have no evidence of cryptosporidiosis. In our ex-vivo model of Cryptosporidium infection, we demonstrated pathophysiological alterations that were blocked by SP-receptor antagonist treatment. Conclusions: These studies suggest that SP-receptor antagonists could prove useful for treatment of AIDS related cryptosporidiosis.