Neutrophil-Microvascular Endothelial Cell Interactions in a Chronic Ethanol Model

慢性乙醇模型中中性粒细胞-微血管内皮细胞的相互作用

基本信息

批准号：
7276203
负责人：
Sonja M Tang
金额：
$ 3.98万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-13 至 2008-04-21
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7276203
关键词：
Acetylcysteine Acute Acute Lung Injury Adherence Adhesions Adult Respiratory Distress Syndrome Alcohol abuse Alcohol consumption Alcohol dependence Alcoholic Beverages Alcohols Alveolar Animal Feed Animals Antioxidants Apoptosis Apoptotic Attenuated Bacteria Bacterial Pneumonia Biology Cell Adhesion Molecules Cell Communication Cessation of life Chronic Clinical Clinical Treatment Communities Consumption Data Diet Dietary Supplementation Disruption Economics Endothelial Cells Endothelium Epidemiologic Studies Epithelial Ethanol Glutathione Goals Half-Life Health Healthcare Systems Hospitals Hypoxemia Individual Infection Inflammation Injury Klebsiella pneumonia bacterium Lead Life Lung Mediating Medical Modeling Necrosis Neutrophil Infiltration Newborn Respiratory Distress Syndrome Outcome Oxidants Oxidative Stress Pathology Patients Phagocytosis Pneumonia Predisposition Production Proteins Pulmonary Edema Rattus Recording of previous events Recruitment Activity Research Respiratory Burst Respiratory Failure Respiratory physiology Risk Risk Factors Role Sepsis Stress Supplementation Testing Therapeutic Time Up-Regulation alcohol effect chronic alcohol ingestion clinically significant cost day drinking drug of abuse feeding insight interstitial killings lung injury macrophage migration mortality neutrophil particle problem drinker protein expression research study response time use

项目摘要

DESCRIPTION (provided by applicant): In recent years our group has shown increasing evidence that chronic alcohol abuse has detrimental effects on lung function; in particular, exacerbation of acute respiratory distress syndrome (ARDS) and increased oxidative stress. In addition, alcohol abusers have an increased mortality when admitted to the hospital with community acquired pneumonia. We question what the underlying pathology of impaired bacterial clearance is that can ultimately lead to death in chronic alcoholics. During bacterial pneumonia, neutrophils are recruited to the alveolar space to phagocytize the infectious particles. Upon phagocytosis, neutrophils undergo apoptosis in order to kill the bacteria. In healthy individuals, macrophage phagocytize the apoptotic neutrophils. In previous studies, we have observed a reduction in macrophage phagocytosis in chronic ethanol-fed animals. We believe this resulting increase in apoptotic neutrophils in the alveolar compartment could be a contributing factor to ARDS and the increased mortality in chronic alcoholics with bacterial pneumonia. In this proposal we will attempt to elucidate the mechanisms of pulmonary neutrophil recruitment and transendothelial migration by examining rolling, adhesion, and migration of neutrophils in real-time using a well-established chronic ethanol model. In addition, we will investigate the effects of Klebsiella pneumoniae infection on neutrophil-endothelial cell interactions. Finally, we will test antioxidant rescue therapies via dietary supplementation with glutathione, N-acetylcysteine, and S-adenosylmethionine. These groups of experiments will provide insight into neutrophil-microvascular endothelial cell interactions and possible therapeutic treatments for chronic alcoholics with community acquired pneumonia.

描述（由申请人提供）：近年来，我们的小组表明越来越多的证据表明慢性酗酒对肺功能有害；特别是，急性呼吸窘迫综合征（ARDS）和氧化应激增加加剧。此外，滥用酗酒者的死亡率增加了，因为社区获得了肺炎。我们质疑细菌清除受损的潜在病理是什么是最终导致慢性酒精中毒死亡。在细菌性肺炎期间，将中性粒细胞募集到肺泡空间中，以吞噬传染性颗粒。吞噬作用后，中性粒细胞会凋亡以杀死细菌。在健康个体中，巨噬细胞吞噬凋亡中性粒细胞。在先前的研究中，我们观察到慢性乙醇喂养动物中巨噬细胞吞噬作用的减少。我们认为，肺泡室中凋亡中性粒细胞的这种增加可能是导致ARD的一个因素，并且慢性酗酒者患有细菌性肺炎的死亡率增加。在此提案中，我们将尝试通过使用良好的慢性乙醇模型实时检查中性粒细胞的滚动，粘附和迁移来阐明肺中性粒细胞募集和跨内皮迁移的机制。此外，我们将研究肺炎肺炎肺炎感染对嗜中性粒细胞 - 内皮细胞相互作用的影响。最后，我们将通过补充谷胱甘肽，N-乙酰半胱氨酸和S-腺苷甲硫代氨酸来测试抗氧化剂救援疗法。这些实验组将提供有关中性粒细胞 - 微血管内皮细胞相互作用的洞察力，以及与社区获得性肺炎的慢性酒精药物的可能治疗方法。