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(改编自申请人的摘要)：临床 沙眼衣原体的临床表现有无症状 粘膜表面感染导致严重疾病 失明、不孕、宫外孕，也许还有关节炎。大有可为 衣原体感染造成的损害被归因于 过度热情的免疫反应限制了病毒的复制 并同时破坏宿主组织。它的确切性质是 对衣原体的保护性和有害的宿主反应仍然存在 没有特征的。同样，细胞因子诱导型一氧化氮(NO)也有 已被发现在体外限制衣原体的复制并发挥作用 在宿主防御其他细胞内病原体中的保护作用 在活体内。它也是一种免疫致病效应分子，在几个 体外和体内系统。它在免疫反应中的确切作用 在体内对衣原体的作用尚未被描述。在研究中 在这项提议之前，我们评估了一口井没有生产- 沙眼衣原体生殖道感染的特征小鼠模型 沙眼衣原体的小鼠生物群。我们发现了深刻的压力 在NO诱导和感染过程中的差异 不同品系的小鼠。NO产量之间的负相关关系 并观察对感染的易感性。因为有相似之处 这一模型与其他哺乳动物模型之间的关系 细胞内的发病机制，我们建议研究一氧化氮的产生 小鼠生殖道衣原体感染及其潜在的作用 保护性分子或致病分子。为了实现这一目标，我们首先提出 将进一步表征尿液动力学的实验 硝酸盐排泄(NO生产的最终产物)在不同的 敏感和耐药品系的小鼠。这将与 感染的过程，炎性组织损伤的发展 在子宫和输卵管中，积水的形成和发育 不孕不育。在这些实验之后，将会有 直接评估NO在保护性免疫反应或 在体内通过抑制NO的产生来损伤炎症 细胞因子诱导型一氧化氮的特异性化学抑制物 合成酶。如果没有保护能力的功能，感染病程 当NO被抑制时，将是长期的或慢性的。如果它演奏了一场大调 在组织破坏中的作用，然后是组织损伤和由此产生的 当不孕症被抑制时，不孕症就会减少。它的目的是 为确定一氧化氮在该模型中的作用而提出的实验 并导致更详细的项目，这些项目详细阐述了分子和 一氧化氮参与衣原体病发病的生化机制 各州。

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