Mechanisms of Lymphatic Pump-Enhancement of Immune Function

淋巴泵的机制——增强免疫功能

基本信息

批准号：
8214696
负责人：
Lisa Michelle Hodge
金额：
$ 35.64万
依托单位：
UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-01-01 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8214696
关键词：
Abdomen Address Advocate Animals Antibodies Antigen-Presenting Cells Antigens Appearance Area Bacteria Blood Blood Circulation Canis familiaris Cell Count Cells Chest Conscious Development Duct (organ) structure Effectiveness Enzyme-Linked Immunosorbent Assay Enzymes Flow Cytometry Foundations Goals Gut associated lymphoid tissue Health Host Defense Immune Immune response Immunity Immunization Immunologic Surveillance Implant In Situ Indwelling Catheter Infection Intestines Investigation Label Leukocyte Trafficking Leukocytes Link Lung Lung diseases Lymph Lymphatic System Lymphocyte Measurement Measures Mesentery Modeling Mucous Membrane Osteopathic manipulation Peripheral Pneumonia Procedures Rattus Reporting Research Role Sampling Source Spleen Streptococcus Techniques Testing Thoracic Duct Tissues Transducers Vaccines White Blood Cell Count procedure adaptive immunity base gastrointestinal immune clearance immune function indexing infectious disease treatment instrument lymph flow lymph nodes lymphatic circulation lymphatic pump novel research study response uptake

项目摘要

DESCRIPTION (provided by applicant): Osteopathic lymphatic pump treatments (LPT) have been advocated for the treatment of infectious disease, and in particular pneumonia, but with no firm scientific foundation. Our preliminary experiments have shown that LPT increases thoracic duct lymph flow and leukocyte concentrations in both rats and dogs. Thus, these initial results support our hypothesis that LPT increases the mobilization and redistribution of leukocyte pools, which may enhance immune surveillance and strengthen host defenses against infection. The proposed investigation will test this hypothesis by accomplishing the following Specific Aims: 1) Determine the tissue source of leukocytes released into lymph and blood during LPT, 2) Determine the distribution of LPT-mobilized leukocytes in peripheral tissues, and 3) Determine if LPT enhances immunity and protection against pulmonary infection. The experiments in Specific Aims 1 and 2 will be conducted in both conscious and anesthetized surgically instrumented dogs. The experiments described in Specific Aim 3 will be conducted in rats. Thoracic duct lymph flow will be measured with an implanted transducer and sampled through an indwelling catheter. Lymph and blood will be collected to determine the regional release of leukocytes and their uptake from blood during LPT. The contribution of the spleen and mucosal tissue will be determined by in situ fluorescently labeling of tissues. Reappearance of labeled leukocytes in lymph will index the repopulation rate of lymph sources sensitive to LPT. Measurements of the rate of appearance and disappearance of leukocytes in blood will be made to determine 1) if leukocytes are released directly into the circulation, particularly from the spleen and gut associated lymphoid tissues, and if LPT may increases this release, and 2) if LPT enhances the return of mobilized leukocytes to tissues. To determine if LPT enhances immunity and protection against pneumonia, rats will be nasally infected with Streptococcus pneumoinae bacteria. We hypothesize that rats receiving LPT will have reduced lung bacteria. To quantify and characterize leukocytes in lymph, blood and tissue, the following analyses and procedures will be used: differential cell counts, flow cytometry, enzyme-linked immunosorbent assay (ELISA), enumeration of antibody forming cells by enzyme-linked immunospot (ELISPOT), and fluorescent labeling of leukocytes. The information gained from this novel investigation will provide a robust scientific basis and rationale for the use of LPT to enhance immunity and treat infection. In addition, this new information will expand basic understanding of the lymphatic system and its role in immunological function. PUBLIC HEALTH REVELANCE: In this proposal we will test the hypothesis that LPT increases the mobilization and redistribution of leukocyte pools, which would enhance immune surveillance and strengthen host defenses against infection. The information gained from this novel investigation will provide a robust scientific basis and rationale for the use of LPT to enhance immunity and treat infection. In addition, this new information will expand basic understanding of the lymphatic system and its role in immunological function.

描述（由申请人提供）：整骨淋巴泵治疗（LPT）已被提倡用于治疗传染病，特别是肺炎，但没有坚实的科学基础。我们的初步实验表明，LPT 可以增加大鼠和狗的胸导管淋巴流量和白细胞浓度。因此，这些初步结果支持我们的假设，即 LPT 增加白细胞库的动员和重新分布，这可能增强免疫监视并增强宿主对感染的防御。拟议的研究将通过实现以下具体目标来检验这一假设：1) 确定 LPT 期间释放到淋巴和血液中的白细胞的组织来源，2) 确定 LPT 动员的白细胞在外周组织中的分布，以及 3) 确定 LPT 是否增强免疫力并预防肺部感染。具体目标 1 和 2 中的实验将在清醒和麻醉的手术犬中进行。具体目标 3 中描述的实验将在大鼠中进行。将使用植入的传感器测量胸导管淋巴流量，并通过留置导管取样。将收集淋巴和血液以确定 LPT 期间白细胞的区域释放及其从血液中的摄取。脾脏和粘膜组织的贡献将通过组织的原位荧光标记来确定。淋巴中标记的白细胞的重新出现将指示对 LPT 敏感的淋巴源的重新增殖率。将测量血液中白细胞的出现和消失率，以确定 1) 白细胞是否直接释放到循环中，特别是从脾脏和肠道相关淋巴组织中释放，以及 LPT 是否会增加这种释放，以及 2) LPT 促进动员的白细胞返回组织。为了确定 LPT 是否增强免疫力和预防肺炎，将对大鼠进行鼻腔感染肺炎链球菌。我们假设接受 LPT 的老鼠肺部细菌会减少。为了量化和表征淋巴、血液和组织中的白细胞，将使用以下分析和程序：分类细胞计数、流式细胞术、酶联免疫吸附测定 (ELISA)、通过酶联免疫斑点 (ELISPOT) 计数抗体形成细胞和白细胞的荧光标记。从这项新颖的调查中获得的信息将为使用 LPT 增强免疫力和治疗感染提供坚实的科学依据和基本原理。此外，这些新信息将扩大对淋巴系统及其在免疫功能中的作用的基本了解。公共卫生启示：在本提案中，我们将检验 LPT 增加白细胞池的动员和重新分布的假设，这将增强免疫监视并增强宿主对感染的防御能力。从这项新颖的调查中获得的信息将为使用 LPT 增强免疫力和治疗感染提供坚实的科学依据和基本原理。此外，这些新信息将扩大对淋巴系统及其在免疫功能中的作用的基本了解。