SUBSTANCE P AND THE PATHOGENESIS OF CRYPTOSPORIDIOSIS IN AIDS

P 物质与艾滋病隐孢子虫病的发病机制

• 批准号: 7958601
• 负责人: PREMA ROBINSON
• 金额: $ 5.81万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958601
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Back; Computer Retrieval of Information on Scientific Projects Database; Cryptosporidiosis; Cryptosporidium; Cryptosporidium parvum; Diarrhea; Enzyme-Linked Immunosorbent Assay; Fluorescence; Funding; Glycine decarboxylase; Grant; Immunohistochemistry; Infection; Institution; Intestines; Life; Macaca; Measures; Messenger RNA; Methods; Microscopy; Modeling; Pathogenesis; Patients; Physiological; Primates; Proteins; Research; Research Personnel; Resources; Role; SIV; Source; Substance P; Substance P Receptor; Techniques; Tissues; United States National Institutes of Health; jejunum; paraform

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.

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