LEWIS ANTIGEN EXPRESSION AND PATHOGENESIS OF H PYORI

幽门螺杆菌的路易斯抗原表达和发病机制

• 批准号: 2887493
• 负责人: Joanna B Goldberg
• 金额: $ 15.22万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887493
• 关键词: Helicobacter; antibody; bacterial cytopathogenic effect; bactericidal immunity; blood group antigens; gastrointestinal disorder; gastrointestinal epithelium; genetic strain; human data; laboratory mouse; nucleic acid sequence; pathologic process; serotyping

Helicobacter pylori is a gram-negative bacterium that lives in the mucus layer of the stomach lining and is the major cause of chronic gastritis and peptic ulcer disease, which is a major risk factor for gastric cancer. The recent realization of the importance of H. pylori as a human pathogen has focused attention on this infectious disease: It is now well established that it is the infection that should be eradicated, not just the symptoms treated. Vaccines composed of whole Helicobacter (either whole-cell sonicates or heat-killed bacterial) alone or in combination with bacterial toxin adjuvant have been shown to provide immunity in several animal models of infection. One major problem with this approach is that factors inherent in H. pylori may cause inflammation and an inappropriate immune response. One such factor is lipopolysaccharide (LPS), which is known to mediate inflammation and induce cytokine release. The structure of the O polysaccharide portion of H. pylori LPS has recently been elucidated for three different strains; each was found to be unique and to terminate in Lewis x and/or Lewis y blood group antigens. H. pylori is the first bacterium found to express these Lewis antigen determinants. Lewis x and Lewis are found on normal gastric tissue but are more abundant on certain tumor cells. Several hypotheses for the role of H. pylori-borne blood group antigens during H. pylori infection can be considered. They may (1) serve as molecular mimics, blinding the host to H. pylori and thereby helping this pathogen to evade the immune system; (2) act as adhesins interacting with cellular receptors on the gastric mucosa; (3) stimulate autoimmune reactions that cause tissue damage and thus contribute to the disease state; or (4) elicit oral tolerance and thus lead to a decreased ability of the host to clear tumors that are also marked by Lewis antigens. None of thee hypotheses is mutually exclusive, nor would any of them fail to contribute to damage to the host. The long-term goal of this new H. pylori research program is to determine the role of Lewis antigens in the pathogenesis and carcinogenic potential of this bacterium. Specifically, a serotyping system for H. pylori based on Lewis antigen expression will be established to type strains from various clinical sources. In addition, H. pylori strains efficient in the production of Lewis antigens will be constructed and evaluated for their pathogenic attributes and their potential as vaccine candidates.

幽门螺杆菌是一种革兰氏阴性细菌， 胃粘膜的粘液层，是慢性 胃炎和消化性溃疡疾病，这是一个主要的危险因素， 胃癌 近年来人们对H.幽门 作为一种人类病原体，人们把注意力集中在这种传染病上： 现在已经很好地确定，应该是感染 根除，而不仅仅是治疗的症状。 疫苗组成 完整螺杆菌（全细胞超声处理或热灭活细菌） 单独或与细菌毒素佐剂组合使用 在几种动物感染模型中提供免疫力。 一个主要 这种方法的问题是H.幽门可能 引起炎症和不适当的免疫反应。 一个这样 因子是脂多糖（LPS），其已知介导 炎症和诱导细胞因子释放。 O的结构 多糖部分。最近已经阐明了幽门螺杆菌LPS 对于三种不同的菌株;每一种都是独特的， 终止于刘易斯x和/或刘易斯y血型抗原。 H.幽门 第一个发现表达这些刘易斯抗原决定簇的细菌。 刘易斯x和刘易斯在正常胃组织中发现，但更多 在某些肿瘤细胞上大量存在 对H. 在H.幽门螺杆菌感染可以是 考虑了 它们可以（1）作为分子模拟物，使宿主失明 到H.幽门螺杆菌，从而帮助这种病原体逃避免疫 系统;（2）作为粘附素与细胞受体相互作用， 胃粘膜;（3）刺激自身免疫反应，导致组织 损害，从而有助于疾病状态;或（4）引起口腔 耐受性，从而导致宿主清除 也被刘易斯抗原标记的肿瘤。 你们谁也别想 假设是相互排斥的，他们中的任何一个都不会失败。 会对宿主造成伤害。 这一新的H. 幽门螺杆菌研究计划的目的是确定刘易斯抗原在 这种细菌的致病机理和致癌潜力。 建立了H.基于刘易斯抗原的幽门螺杆菌 将建立表达以分型来自各种临床的菌株， 源 此外，H.幽门螺杆菌菌株有效地生产 将构建刘易斯抗原并评估其致病性 其特性及其作为候选疫苗的潜力。