Mechanisms of Lymphatic Pump-Enhancement of Immune Function

淋巴泵的机制——增强免疫功能

• 批准号: 7530830
• 负责人: Lisa Michelle Hodge
• 金额: $ 36万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7530830
• 关键词: Abdomen; Address; Advocate; Animals; Antibodies; Antigen-Presenting Cells; Antigens; Appearance; Area; Bacteria; Blood; Blood Circulation; Canis familiaris; Cell Count; Cells; Chest; Communicable Diseases; Conscious; Development; Duct (organ) structure; Effectiveness; Enzyme-Linked Immunosorbent Assay; Enzymes; Flow Cytometry; Foundations; Goals; 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; Public Health; Reporting; Research; Role; Sampling; Source; Spleen; Techniques; Testing; Thoracic Duct; Thymus Gland; Tissues; Transducers; Vaccines; White Blood Cell Count procedure; base; gastrointestinal; immune function; indexing; infectious disease treatment; instrument; lymph flow; lymph nodes; lymphatic circulation; lymphatic pump; novel; research study; response; uptake

DESCRIPTION (provided by applicant): We were the first to demonstrate that osteopathic lymphatic pump treatments (LPT) increase lymph flow. LPT has long been advocated for the treatment of infectious disease, and in particular pneumonia, but with no firm scientific foundation. Now our Preliminary experiments also show that LPT increases leukocyte count in thoracic duct lymph and blood. Thus, these initial results support our hypothesis that LPT increases the mobilization and redistribution of leukocyte pools, which would 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 adaptive immunity and protection from pulmonary challenge. Experiments will be conducted in both conscious and anesthetized surgically instrumented dogs. 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, thymus and mucosal tissue will be determined by in situ fluorescent 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 thymus gland, and if LPT may increase this release, and 2) if LPT may enhance the return of mobilized leukocytes to tissues. To determine if LPT enhances vaccine-specific immunity and protection from infectious disease, immunized dogs will be challenged with pulmonary infection. We hypothesize that dogs 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）：我们是第一个证明骨质淋巴泵处理（LPT）会增加淋巴流量的人。长期以来，LPT一直在倡导治疗传染病，尤其是肺炎，但没有牢固的科学基础。现在，我们的初步实验还表明，LPT增加了胸管淋巴和血液中的白细胞计数。因此，这些最初的结果支持我们的假设，即LPT增加了白细胞池的动员和重新分布，这将增强免疫监测并增强宿主防御感染。提出的研究将通过实现以下特定目的来检验这一假设：1）确定在LPT期间释放成淋巴和血液的白细胞的组织来源，2）确定LPT-Mobilized白细胞在外周组织中的分布，3）确定LPT是否增强了适应性免疫和保护肺部挑战。实验将在有意识和麻醉的手术仪器中进行。胸管淋巴流将通过植入的换能器测量，并通过留置导管进行采样。将收集淋巴和血液，以确定白细胞的区域释放及其在LPT期间从血液中摄取。脾脏，胸腺和粘膜组织的贡献将通过组织的原位荧光标记来确定。淋巴标记的白细胞的重新出现将指定对LPT敏感的淋巴源的重生速率。白细胞在血液中的外观速率和消失的测量将确定1）如果直接释放了白细胞，尤其是从脾脏和胸腺中释放到循环中，并且LPT可能会增加此释放，并且2）如果LPT可能会增强动员的白细胞回归组织到组织。为了确定LPT是否增强了疫苗特异性免疫和免受传染病的保护，免疫犬将受到肺部感染的挑战。我们假设接受LPT的狗会减少肺细菌。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：差异细胞计数，流式细胞术，酶联免疫吸收测定法（ELISA），抗体形成细胞的枚举，通过酶联免疫离子替代（ELISPOT（ELISPOT）和FLEORETENT）和FLEORESTENT。从这项新型研究中获得的信息将为使用LPT增强免疫力和治疗感染提供强大的科学基础和理由。此外，这些新信息将扩展对淋巴系统及其在免疫功能中的作用的基本理解。 公共卫生的启示：在此提案中，我们将检验以下假设：LPT增加了白细胞池的动员和重新分布，这将增强免疫监测并加强宿主防御感染感染。从这项新型研究中获得的信息将为使用LPT增强免疫力和治疗感染提供强大的科学基础和理由。此外，这些新信息将扩展对淋巴系统及其在免疫功能中的作用的基本理解。