Systems biology of lymphatic transport

淋巴运输的系统生物学

基本信息

批准号：
8927855
负责人：
LANCE L MUNN
金额：
$ 59.59万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8927855
关键词：
Adopted Adverse effects Affect Animal Model Bacterial Infections Beds Behavior Biological Calcium Calcium Channel Blockers Caliber Cardiovascular system Computer Simulation Diffusion Disease Drainage procedure Edema Equilibrium Failure Feedback Force of Gravity Frequencies Functional disorder Goals Heart Hindlimb Homeostasis Housing Immune System Diseases Immune response Individual Infection Inflammation Kinetics Knockout Mice Liquid substance Lymph Lymphatic Lymphatic System Lymphatic vessel Mechanics Mediating Modeling Morbidity - disease rate Movement Mus Nitric Oxide Nitric Oxide Signaling Pathway Pathology Pathway interactions Patients Performance Peripheral Physiology Play Production Pump Reaction Relaxation Role Specific qualifier value Sterility System Systems Biology Testing Tissues Water drug candidate effective therapy fluid flow interstitial intravital imaging lymph flow lymph nodes lymphatic pump mathematical model mouse model multi-scale modeling novel novel strategies pressure prevent public health relevance response simulation treatment strategy vasomotion

项目摘要

DESCRIPTION (provided by applicant): Lymphatic vessels can transport fluid either by pressure-driven flow or by active pumping, even against gravity when necessary. In normal physiology, the lymphatic system is able to use these mechanisms to effectively and dynamically maintain tissue fluid homeostasis. In some diseases, however, lymphatic function is inefficient, resulting in tissue edema and weakened immune response. Because the mechanisms that control lymphatic function are not well-understood, we currently have no effective therapies that can restore lymphatic function in these patients. We propose that transport of lymph is controlled by complementary mechanobiological mechanisms involving Ca2+ fluxes and nitric oxide. We will test this hypothesis by developing a computational model of lymphatic transport and tissue fluid dynamics. We will then validate the simulations in a mouse model of lymphatic function and use it to identify and test novel treatments for edema and impaired lymph flow.

描述（由申请人提供）：淋巴管可以通过压力驱动流或主动泵送液体，甚至在必要时抵抗重力。在正常生理学中，淋巴系统能够使用这些机制来有效和动态地维持组织液稳态。然而，在某些疾病中，淋巴功能低下，导致组织水肿和免疫反应减弱，因为控制淋巴功能的机制尚不清楚，目前我们没有有效的疗法可以恢复。我们认为，淋巴液的转运是由涉及 Ca2+ 通量和一氧化氮的互补机械生物学机制控制的，然后我们将通过开发淋巴转运和组织液动力学的计算模型来验证这一假设。淋巴功能的小鼠模型，并用它来识别和测试针对水肿和淋巴液流动受损的新疗法。