The lymphatic vascular system is a highly organized network of structurally and functionally connected specialized lymphatic vessels of various sizes and lymph nodes that perform metabolic and transport functions. Lymph is a blood plasma filtrate that comprises antigen-presenting cells and lymphocytes. Via lymph, excess fluid and extravasated proteins are removed from the tissues. The lymphatic system supports an extracellular fluid homeostasis that is favorable for optimal tissue functioning by removing substances that result from metabolism or cell death, as well as optimizing immunity against bacteria, viruses and other antigens. Although the lymphatic vasculature is not formally considered part of the immune system, it is crucial for the traffic of antigens and immune cells. In addition, lymphatic endothelial cells can supply antigens and express factors that modulate immune responses. After an inflammatory stimulus, endothelial cells produce chemokines, which recruit immune cells to the lymph nodes. Unlike the circulatory system with a centralized pump, the movement of lymph through the network of lymphatic vessels is provided by forces that stimulate the initial formation of lymph in the tissues and the ability of the lymphatic vessels and nodes to rhythmically contract, providing increased pressure and lymph movement in the proximal direction. Since the metabolic rate in various organs and tissues varies significantly depending on the functional state of the tissue, the blood flow through the tissue and the amount of lymph formed also change significantly. The lymphatic vasculature has several circuits for regulating lymph flow. This review provides a comprehensive overview of the important results obtained over the past century and discusses the molecular and physiological control of the transport function of lymphatic vessels and nodes.
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