Interaction between leukotoxin and RBCs

白细胞毒素和红细胞之间的相互作用

• 批准号: 7559107
• 负责人: SCOTT C KACHLANY
• 金额: $ 23.4万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ DENTAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-22 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7559107
• 关键词: Actinobacillus actinomycetemcomitans; Affinity Chromatography; Bacteria; Binding; Blood Cells; Cell Surface Proteins; Cell surface; Cytolysis; Disease; Epitopes; Erythrocytes; Goals; Hemolysis; Human; Human Identifications; Immune response; Immunotoxins; Infection; Infective endocarditis; Lead; Leukocytes; Monoclonal Antibodies; Oral; Pathogenesis; Periodontitis; Play; Primates; Proteins; Role; Systemic disease; Systemic infection; Therapeutic Agents; Toxin; design; leukotoxin; mortality; neutralizing monoclonal antibodies; pathogen; public health relevance; receptor; research study

DESCRIPTION: Aggregatibater (Actinobacillus) actinomycetemcomitans is the etiologic agent of localized aggressive periodontitis and other systemic infections including infective endocarditis. A. actinomycetemcomitans produces an RTX toxin, leukotoxin (LtxA), specific for human and primate blood cells. LtxA acts as an immunotoxin, helping the bacterium to evade the immune response. We recently discovered that LtxA can lyse human red blood cells (RBCs) and have shown that this new function may play an important role in pathogenesis. Virtually nothing is known about the interactions between LtxA and RBCs since we only recently made this observation. The proposed experiments are designed to characterize and define the molecular interactions between LtxA and RBCs. We propose to first identify the RBC receptor for LtxA and next to define the domains of LtxA that are involved in binding to RBCs. Identifying critical interactions between LtxA and host RBCs may lead to the design of therapeutic agents that block interaction and subsequent disease. PUBLIC HEALTH RELEVANCE: The oral and systemic pathogen, Aggregatibater (Actinobacillus) actinomycetemcomitans, produces a toxin (leukotoxin) that targets human blood cells. Very little is known about the molecular interactions between the toxin and red blood cells (RBCs). Our goals are to identify and characterize the RBC receptor and domains in leukotoxin that are important for the toxin to bind RBCs.

描述：聚集巴生（肌动杆菌）放线菌CETEMCOMITANS是局部攻击性牙周炎和其他全身感染（包括感染性心内膜炎）的病因学药。 A.放线症患者会产生RTX毒素，白细胞毒素（LTXA），该毒素针对人类和灵长类动物的血细胞。 LTXA充当免疫毒素，有助于细菌逃避免疫反应。我们最近发现LTXA可以裂解人类红细胞（RBC），并表明该新功能在发病机理中可能起重要作用。自从我们直到最近才对LTXA和RBC之间的相互作用，几乎一无所知。所提出的实验旨在表征和定义LTXA和RBC之间的分子相互作用。我们建议首先识别LTXA的RBC受体，然后定义与RBC结合的LTXA域。确定LTXA与宿主RBC之间的关键相互作用可能会导致设计阻断相互作用和随后疾病的治疗剂。公共卫生相关性：口服和全身性病原体，聚集巴生（肌动杆菌）放线症cotemcitans，产生靶向人体血细胞的毒素（白细胞毒素）。关于毒素和红细胞（RBC）之间的分子相互作用知之甚少。我们的目标是识别和表征白细胞毒素中的RBC受体和域，这对于毒素结合RBC很重要。