NITRIC OXIDE AND CHLAMYDIAL INFECTIONS OF MICE

小鼠的一氧化氮和衣原体感染

• 批准号: 2074678
• 负责人: Kyle H. Ramsey
• 金额: $ 9.94万
• 依托单位: MIDWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2074678
• 关键词: Chlamydia trachomatis; bactericidal immunity; chlamydial disease; disease /disorder model; fallopian tubes; female; fertility; genetic strain; genetically modified animals; histopathology; inflammation; laboratory mouse; nitrates; nitric oxide; nitric oxide synthase; urinalysis; uterus

DESCRIPTION (Adapted from the applicant's abstract): The clinical manifestations of Chlamydia trachomatis range from asymptomatic infections of mucosal surfaces to severe disease that results in blindness, infertility, ectopic pregnancy, and perhaps arthritis. Much of the damage resulting from chlamydial infection has been attributed to an overzealous immune response that limits replication of the organism and concurrently destroys host tissues. The exact nature of the protective and deleterious host responses against chlamydia remain uncharacterized. Similarly, cytokine inducible nitric oxide (NO) has been found to limit the replication of chlamydia in vitro and to play a protective role in host defense against other intracellular pathogens in vivo. It also is as an immunopathogenic effector molecule in several in vitro and in vivo systems. Its exact role in immune responses against chlamydia in vivo has yet to be delineated. In studies preliminary to this proposal, we assessed NO production in a well- characterized murine model of chlamydial genital tract infection with the mouse biovar of Chlamydia trachomatis. We found profound strain differences in the induction of NO and in the course of infection in different strains of mice. An inverse correlation between NO production and susceptibility to infection was observed. Because of the parallels between this model and other mammalian models of NO-mediated intracellular pathogenesis, we propose to study NO production following chlamydial genital tract infection of mice and its role as a potential protective or pathogenic molecule. To accomplish this, we first propose experiments which will further characterize the kinetics of urinary nitrate excretion (an end product of NO production) in various susceptible and resistant strains of mice. This will be correlated with the course of infection, the development of inflammatory tissue damage in the uterus and oviduct, hydrosalpinx formation, and the development of infertility. These experiments will be followed by those which directly assess the role of NO in either protective immune responses or in damaging inflammation by inhibiting the production of NO in vivo with specific chemical inhibitors of the cytokine inducible nitric oxide synthase. If NO functions in a protective capacity, the infection course will be prolonged or chronic when NO is inhibited. If it plays a major role in tissue destruction, then tissue damage and the resulting infertility will be reduced when it is inhibited. It is the purpose of the proposed experiments to characterize the role of NO in this model and lead to more detailed projects that elaborate the molecular and biochemical mechanisms of NO-mediated pathogenesis in chlamydial disease states.

描述（改编自申请人摘要）：临床 沙眼衣原体的表现从无症状 从粘膜表面感染到严重疾病， 失明、不孕、宫外孕，也许还有关节炎。多 衣原体感染所造成的损害 过度的免疫反应限制了 生物体并同时破坏宿主组织。的确切性质 对衣原体保护性和有害的宿主反应仍然存在 没有特征的类似地，细胞因子诱导型一氧化氮（NO）具有 已经发现限制体外衣原体的复制， 在宿主防御其他细胞内病原体中的保护作用 in vivo.它也是一种免疫致病效应分子， 体外和体内系统。它在免疫反应中的确切作用 体内抗衣原体的作用还有待描述。研究中 在此建议的初步阶段，我们评估了一口井的NO产量- 衣原体生殖道感染的特征性小鼠模型， 沙眼衣原体的小鼠生物变种我们发现了巨大的压力 NO诱导和感染过程中的差异， 不同品系的老鼠NO生成量与 并观察对感染的易感性。因为这些相似之处 这种模型和其他哺乳动物模型之间的NO介导的 细胞内发病机制，我们建议研究NO生产以下 小鼠生殖道衣原体感染及其作为一种潜在的 保护或致病分子。为了实现这一目标，我们首先提出 将进一步表征尿动力学的实验 硝酸盐排泄（NO产生的最终产物）在各种 敏感和耐药品系的小鼠。这将与 感染过程中，炎症组织损伤的发展 输卵管积水的形成和发育 不孕症的症状这些实验之后， 直接评估NO在保护性免疫反应中的作用， 通过抑制体内NO的产生来破坏炎症， 细胞因子诱导型一氧化氮的特异性化学抑制剂 合成酶如果NO起保护作用， 当NO被抑制时，将延长或慢性化。如果它演奏大调 在组织破坏中的作用，然后是组织损伤， 抑制不孕症就会减少。才是目的 提出的实验来表征NO在这个模型中的作用 并导致更详细的项目，阐述分子和 一氧化氮介导的衣原体病发病机制的生化机制 states.

项目成果

Inducible nitric oxide synthase does not affect resolution of murine chlamydial genital tract infections or eradication of chlamydiae in primary murine cell culture.

诱导型一氧化氮合酶不影响小鼠衣原体生殖道感染的解决或原代小鼠细胞培养物中衣原体的根除。

• DOI: 10.1128/iai.66.2.835-838.1998
• 发表时间: 1998
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Ramsey,KH;Miranpuri,GS;Poulsen,CE;Marthakis,NB;Braune,LM;Byrne,GI
• 通讯作者: Byrne,GI

The in vitro antimicrobial capacity of human colostrum against Chlamydia trachomatis.

人初乳对沙眼衣原体的体外抗菌能力。

• DOI: 10.1016/s0165-0378(98)00010-2
• 发表时间: 1998
• 期刊: Journal of reproductive immunology
• 影响因子: 3.4
• 作者: Ramsey,KH;Poulsen,CE;Motiu,PP
• 通讯作者: Motiu,PP

Inducible nitric oxide synthase regulates production of isoprostanes in vivo during chlamydial genital infection in mice.

诱导型一氧化氮合酶在小鼠衣原体生殖器感染期间调节体内异前列腺素的产生。

• DOI: 10.1128/iai.71.12.7183-7187.2003
• 发表时间: 2003
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Ramsey,KH;Sigar,IM;Rana,SV;Gupta,J;Holland,SM;Byrne,GI;Morrow,JD
• 通讯作者: Morrow,JD