microcirculationРегионарное кровообращение и микроциркуляцияRegional blood circulation and microcirculation1682-66552712-9756Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1682-6655-2020-19-3-5-18microcirculation-843Research ArticleОБЗОРЫREVIEWSСтруктура и физиология лимфатической сосудистой сетиStructure and physiology of the lymphatic vasculatureЛобовГ. И.LobovG. I.

Лобов Геннадий Иванович – д-р мед. наук, профессор, зав. лабораторией физиологии сердечно-сосудистой и лимфатической систем

199034, Санкт-Петербург, наб. Макарова, д. 6

Lobov Gennady I. – MD, Professor, Head Laboratory of Physiology of Cardiovascular and Lymphatic Systems

6, Makarova street, Saint Petersburg, 199034

gilobov@yandex.ruНепиющихЖ. В.NepiyushchikhZh. V.

Непиющих Жанна Вячеславовна – научный сотрудник лаборатории физиологии сердечно-сосудистой и лимфатической систем

199034, Санкт-Петербург, наб. Макарова, д. 6

Nepiyushchikh Zhanna V. – MD, Research Scientist II, Laboratory of Physiology of Cardiovascular and Lymphatic Systems

6, Makarova street, Saint Petersburg, 199034

nezhanna@gmail.comФедеральное государственное бюджетное учреждение науки «Институт физиологии имени И. П. Павлова» Российской академии наукРоссияPavlov Institute of Physiology of the Russian Academy of SciencesRussian Federation202007102020193518Copyright © Лобов Г.И., Непиющих Ж.В., 20202020Лобов Г.И., Непиющих Ж.В.Lobov G.I., Nepiyushchikh Z.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.microcirc.ru/jour/article/view/843

Лимфатическая сосудистая система представляет собой высокоорганизованную сеть структурно и функционально связанных специализированных лимфатических сосудов разного калибра и лимфатических узлов, которые выполняют обменные и транспортные функции. Лимфа – это образующийся в тканях фильтрат плазмы крови, в котором содержатся антигенпрезентирующие клетки и лимфоциты. С лимфой из тканей удаляются избыток жидкости и экстравазированные белки. Лимфатическая система поддерживает гомеостаз внеклеточной жидкости, благоприятный для оптимальной функции тканей, удаляя вещества, которые возникают в результате метаболизма или гибели клеток, а также оптимизируя иммунитет против бактерий, вирусов и других антигенов. Несмотря на то, что лимфатическая сосудистая сеть формально не считается частью иммунной системы, она имеет решающее значение для трафика антигенов и иммунных клеток. Помимо этого, лимфатические эндотелиальные клетки способны представлять антигены и экспрессировать факторы, модулирующие иммунные реакции. После воспалительного стимула эндотелиальные клетки вырабатывают хемокины, которые рекрутируют иммунные клетки в лимфатические узлы. В отличие от системы кровообращения с централизованным насосом, движение лимфы через сеть лимфатических сосудов обеспечивается силами, стимулирующими первоначальное образование лимфы в тканях и способностью лимфатических сосудов и узлов ритмично сокращаться, обеспечивая повышение давления и перемещение лимфы в проксимальном направлении. Поскольку скорость метаболизма в различных органах и тканях значительно изменяется в зависимости от функционального состояния ткани, также существенно изменяется и кровоток через ткань и количество образующейся лимфы. Лимфатическая сосудистая сеть имеет несколько контуров регуляции лимфотока. В данной статье представлен всесторонний обзор важных результатов, полученных за прошедшее столетие, и обсуждается молекулярный и физиологический контроль транспортной функции лимфатических сосудов и узлов.

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.

лимфатические сосудылимфатические узлылимфотокгладкомышечные клеткиэндотелийрегуляцияlymphatic vesselslymph nodeslymph flowsmooth muscle cellsendotheliumregulationReferencesBernaudin JF, Kambouchner M, Lacave R. Lymphatic vascular system, development and lymph formation. Review. Rev Pneumol Clin. 2013;69(2):93–101. Doi: 10.1016/j.pneumo.2013.01.005.Bernaudin JF, Kambouchner M, Lacave R. Lymphatic vascular system, development and lymph formation. Review. Rev Pneumol Clin. 2013;69(2):93–101. Doi: 10.1016/j.pneumo.2013.01.005.Plog BA, Nedergaard M. The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future. Annu Rev Pathol. 2018;13:379–394. Doi: 10.1146/annurev-pathol-051217-111018.Plog BA, Nedergaard M. The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future. Annu Rev Pathol. 2018;13:379–394. Doi: 10.1146/annurev-pathol-051217-111018.Park PJ, Chang M, Garg N, Zhu J, Chang JH, Shukla D. Corneal lymphangiogenesis in herpetic stromal keratitis. Surv Ophthalmol. 2015;60(1):60–71. Doi: 10.1016/j.survophthal.2014.06.001.Park PJ, Chang M, Garg N, Zhu J, Chang JH, Shukla D. Corneal lymphangiogenesis in herpetic stromal keratitis. Surv Ophthalmol. 2015;60(1):60–71. Doi: 10.1016/j.survophthal.2014.06.001.Mendoza E, Schmid-Schonbein GW. A model for mechanics of primary lymphatic valves. J Biomech Eng. 2003;125: 407–414. Doi: 10.1115/1.1568128.Mendoza E, Schmid-Schonbein GW. A model for mechanics of primary lymphatic valves. J Biomech Eng. 2003;125: 407–414. Doi: 10.1115/1.1568128.Leak LV, Burke JF. Ultrastructural studies on the lymphatic anchoring filaments. J Cell Biol. 1968;36(1):129–149.Leak LV, Burke JF. Ultrastructural studies on the lymphatic anchoring filaments. J Cell Biol. 1968;36(1):129–149.Aukland K, Reed RK. Interstitial-lymphatic mechanisms in the control of extracellular fluid volume. Physiol Rev. 1993;73(1):1–78. Doi: 10.1152/physrev.1993.73.1.1.Aukland K, Reed RK. Interstitial-lymphatic mechanisms in the control of extracellular fluid volume. Physiol Rev. 1993;73(1):1–78. Doi: 10.1152/physrev.1993.73.1.1.Michel CC. Starling: the formulation of his hypothesis of microvascular fluid exchange and its significance after 100 years. Exp Physiol. 1997;82:1–30. Doi: 10.1113/expphysiol.1997.sp004000.Michel CC. Starling: the formulation of his hypothesis of microvascular fluid exchange and its significance after 100 years. Exp Physiol. 1997;82:1–30. Doi: 10.1113/expphysiol.1997.sp004000.Bert JL, Reed RK. Flow conductivity of rat dermis is determined by hydration. Biorheology. 1995;32(1):17–27. Doi: 10.3233/bir-1995-32102.Bert JL, Reed RK. Flow conductivity of rat dermis is determined by hydration. Biorheology. 1995;32(1):17–27. Doi: 10.3233/bir-1995-32102.Schmid-Schonbein GW. Microlymphatics and lymph flow. Physiol Rev. 1990;70(4):987–1028. Doi: 10.1152/physrev.1990.70.4.987.Schmid-Schonbein GW. Microlymphatics and lymph flow. Physiol Rev. 1990;70(4):987–1028. Doi: 10.1152/physrev.1990.70.4.987.Dixon JB, Raghunathan S, Swartz MA. A tissue-engineered model of the intestinal lacteal for evaluating lipid transport by lymphatics. Biotechnol Bioeng. 2009;103(6):12241235. Doi: 10.1002/bit.22337.Dixon JB, Raghunathan S, Swartz MA. A tissue-engineered model of the intestinal lacteal for evaluating lipid transport by lymphatics. Biotechnol Bioeng. 2009;103(6):12241235. Doi: 10.1002/bit.22337.Bohlen HG, Unthank JL. Rat intestinal lymph osmolarity during glucose and oleic acid absorption. Am J Physiol. 1989;257(3 Pt 1):G438–G446. Doi: 10.1152/ajpgi.1989.257.3.G438.Bohlen HG, Unthank JL. Rat intestinal lymph osmolarity during glucose and oleic acid absorption. Am J Physiol. 1989;257(3 Pt 1):G438–G446. Doi: 10.1152/ajpgi.1989.257.3.G438.Fadnes HO. Colloid osmotic pressure in interstitial fluid and lymph from rabbit subcutaneous tissue. Microvasc Res. 1981;21(3):390–392. Doi: 10.1016/0026-2862(81)90022-4.Fadnes HO. Colloid osmotic pressure in interstitial fluid and lymph from rabbit subcutaneous tissue. Microvasc Res. 1981;21(3):390–392. Doi: 10.1016/0026-2862(81)90022-4.Dzieciatkowska M, Wohlauer MV, Moore EE, Damle S, Peltz E, Campsen J, Kelher M, Silliman C, Banerjee A, Hansen KC. Proteomic analysis of human mesenteric lymph. Shock. 2011;35(4):331–338. Doi: 10.1097/SHK.0b013e318206f654.Dzieciatkowska M, Wohlauer MV, Moore EE, Damle S, Peltz E, Campsen J, Kelher M, Silliman C, Banerjee A, Hansen KC. Proteomic analysis of human mesenteric lymph. Shock. 2011;35(4):331–338. Doi: 10.1097/SHK.0b013e318206f654.Vinuesa CG, Chang PP. Innate B cell helpers reveal novel types of antibody responses. Nat Immunol. 2013;14(2): 119–126. Doi: 10.1038/ni.2511.Vinuesa CG, Chang PP. Innate B cell helpers reveal novel types of antibody responses. Nat Immunol. 2013;14(2): 119–126. Doi: 10.1038/ni.2511.Borisov AV. Functional anatomy of lymphangion. Morfologiia. 2005;128(6):18–27.Borisov AV. Functional anatomy of lymphangion. Morfologiia. 2005;128(6):18–27.D’Andrea V, Panarese A, Taurone S, Coppola L, Cavallotti C, Artico M. Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic and NPYergic Nerve Fibers. Lymphat Res Biol. 2015;13(3):170–175. Doi: 10.1089/lrb.2015.0018.D’Andrea V, Panarese A, Taurone S, Coppola L, Cavallotti C, Artico M. Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic and NPYergic Nerve Fibers. Lymphat Res Biol. 2015;13(3):170–175. Doi: 10.1089/lrb.2015.0018.Borisov AV. The theory of the design of the lymphangion. Morfologiia. 1997;112(5):7–17.Borisov AV. The theory of the design of the lymphangion. Morfologiia. 1997;112(5):7–17.Mazzoni MC, Skalak TC, Schmid-Schonbein GW. Structure of lymphatic valves in the spinotrapezius muscle of the rat. Blood Vessels. 1987; 24(6):304–312. Doi: 10.1159/000158707.Mazzoni MC, Skalak TC, Schmid-Schonbein GW. Structure of lymphatic valves in the spinotrapezius muscle of the rat. Blood Vessels. 1987; 24(6):304–312. Doi: 10.1159/000158707.Riquet M, Le Pimpec Barthes F, Souilamas R, Hidden G. Thoracic duct tributaries from intrathoracic organs. Ann Thorac Surg. 2002;73(3):892–898; discussion 898-899. Doi: 10.1016/s0003-4975(01)03361-6.Riquet M, Le Pimpec Barthes F, Souilamas R, Hidden G. Thoracic duct tributaries from intrathoracic organs. Ann Thorac Surg. 2002;73(3):892–898; discussion 898-899. Doi: 10.1016/s0003-4975(01)03361-6.Granger DN. Intestinal microcirculation and transmucosal fluid transport. Am J Physiol. 1981;240(5):G343–G349. Doi: 10.1152/ajpgi.1981.240.5.G343.Granger DN. Intestinal microcirculation and transmucosal fluid transport. Am J Physiol. 1981;240(5):G343–G349. Doi: 10.1152/ajpgi.1981.240.5.G343.Kohan AB, Yoder SM, Tso P. Using the lymphatics to study nutrient absorption and the secretion of gastrointestinal hormones. Physiol Behav. 2011;30;105(1):82–88. Doi: 10.1016/j.physbeh.2011.04.056.Kohan AB, Yoder SM, Tso P. Using the lymphatics to study nutrient absorption and the secretion of gastrointestinal hormones. Physiol Behav. 2011;30;105(1):82–88. Doi: 10.1016/j.physbeh.2011.04.056.Azzali G. Structure, lymphatic vascularization and lymphocyte migration in mucosa-associated lymphoid tissue. Immunol Rev. 2003;195:178–189. Doi: 10.1034/j.1600-065x.2003.00072.x.Azzali G. Structure, lymphatic vascularization and lymphocyte migration in mucosa-associated lymphoid tissue. Immunol Rev. 2003;195:178–189. Doi: 10.1034/j.1600-065x.2003.00072.x.Nestle FO, Di Meglio P, Qin JZ, Nickoloff BJ. Skin immune sentinels in health and disease. Nat Rev Immunol. 2009;9(10):679–691. Doi: 10.1038/nri2622.Nestle FO, Di Meglio P, Qin JZ, Nickoloff BJ. Skin immune sentinels in health and disease. Nat Rev Immunol. 2009;9(10):679–691. Doi: 10.1038/nri2622.Wang XN, McGovern N, Gunawan M, Richardson C, Windebank M, Siah TW, Lim HY, Fink K, Li JL, Ng LG, Ginhoux F, Angeli V, Collin M, Haniffa M. A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels. J Invest Dermatol. 2014;134(4):965–974. Doi: 10.1038/jid.2013.481.Wang XN, McGovern N, Gunawan M, Richardson C, Windebank M, Siah TW, Lim HY, Fink K, Li JL, Ng LG, Ginhoux F, Angeli V, Collin M, Haniffa M. A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels. J Invest Dermatol. 2014;134(4):965–974. Doi: 10.1038/jid.2013.481.Leak LV, Jamuar MP. Ultrastructure of pulmonary lymphatic vessels. Am Rev Respir Dis. 1983;128(2 Pt 2):S59–65. Doi: 10.1164/arrd.1983.128.2P2.S59.Leak LV, Jamuar MP. Ultrastructure of pulmonary lymphatic vessels. Am Rev Respir Dis. 1983;128(2 Pt 2):S59–65. Doi: 10.1164/arrd.1983.128.2P2.S59.Weber E, Sozio F, Borghini A, Sestini P, Renzoni E. Pulmonary lymphatic vessel morphology: a review. Ann Anat. 2018;218:110–117. Doi: 10.1016/j.aanat.2018.02.011.Weber E, Sozio F, Borghini A, Sestini P, Renzoni E. Pulmonary lymphatic vessel morphology: a review. Ann Anat. 2018;218:110–117. Doi: 10.1016/j.aanat.2018.02.011.Лобов Г. И. Роль лимфатической системы в гомеостазе интерстициальной жидкости в легких и плевральной жидкости // Регионар. кровообращение и микроциркуляция. – 2019. –Т. 18, № 1. – С. 104–112. Doi: 10.24884/1682-6655-2019-18-1-104-112.Lobov GI. The role of the lymphatic system in the homeostasis of the interstitial fluid in the lung and pleural liquid. Regional blood circulation and microcirculation. 2019;18(1):104–112. (In Russ.). Doi: 10.24884/1682-6655-2019-18-1-104-112.Zweifach BW, Prather JW. Micromanipulation of pressure in terminal lymphatics in the mesentery. Am J Physiol. 1975;228(5):1326–1335. Doi: 10.1152/ajplegacy.1975.228.5.1326.Zweifach BW, Prather JW. Micromanipulation of pressure in terminal lymphatics in the mesentery. Am J Physiol. 1975;228(5):1326–1335. Doi: 10.1152/ajplegacy.1975.228.5.1326.Лобов Г. И., Орлов Р. С. Саморегуляция насосной функции лимфангиона // Физиол. журн. СССР им. И. М. Сеченова. – 1988. – Т. 74, № 7. – С. 977–986.Lobov GI, Orlov RS. Self-regulation of the pumping function of the lymphangion. Fiziologicheskii zhurnal SSSR im. I. M. Sechenova. 1988;74(7):977–986. (In Russ.).Razavi MS, Nelson TS, Nepiyushchikh Z, Gleason RL, Dixon JB. The relationship between lymphangion chain length and maximum pressure generation established through in vivo imaging and computational modeling. Am. J. Physiol. Heart Circ. Physiol. 2017;313(6):H1249–H1260. Doi: 10.1152/ajpheart.00003.2017.Razavi MS, Nelson TS, Nepiyushchikh Z, Gleason RL, Dixon JB. The relationship between lymphangion chain length and maximum pressure generation established through in vivo imaging and computational modeling. Am. J. Physiol. Heart Circ. Physiol. 2017;313(6):H1249–H1260. Doi: 10.1152/ajpheart.00003.2017.Lobov GI. The Rheological Properties of the Large Lymphatic Vessels. Fiziologicheskii zhurnal SSSR im. I. M. Sechenova. 1990;76(3):371–377. (In Russ.).Lobov GI. The Rheological Properties of the Large Lymphatic Vessels. Fiziologicheskii zhurnal SSSR im. I. M. Sechenova. 1990;76(3):371–377. (In Russ.).Crowe MJ, von der Weid PY, Brock JA, Van Helden DF. Coordination of contractile activity in guinea-pig mesenteric lymphatics. J Physiol. 1997;500( Pt 1)(Pt 1):235–244. Doi: 10.1113/jphysiol.1997.sp022013.Crowe MJ, von der Weid PY, Brock JA, Van Helden DF. Coordination of contractile activity in guinea-pig mesenteric lymphatics. J Physiol. 1997;500( Pt 1)(Pt 1):235–244. Doi: 10.1113/jphysiol.1997.sp022013.Breslin JW. Mechanical forces and lymphatic transport. Microvasc Res. 2014;96:46–54. Doi: 10.1016/j.mvr.2014.07.013.2014.Breslin JW. Mechanical forces and lymphatic transport. Microvasc Res. 2014;96:46–54. Doi: 10.1016/j.mvr.2014.07.013.2014.Zawieja DC. Contractile Physiology of Lymphatics. Lymphat Res Biol. 2009;7(2):87–96. Doi: 10.1089/lrb.2009.0007.Zawieja DC. Contractile Physiology of Lymphatics. Lymphat Res Biol. 2009;7(2):87–96. Doi: 10.1089/lrb.2009.0007.Orlov RS, Lobov GI. Ionic mechanisms of the electrical activity of the smooth-muscle cells of the lymphatic vessels. Fiziologicheskii zhurnal SSSR im. I. M. Sechenova. 1984; 70(5):712–721. (In Russ.).Orlov RS, Lobov GI. Ionic mechanisms of the electrical activity of the smooth-muscle cells of the lymphatic vessels. Fiziologicheskii zhurnal SSSR im. I. M. Sechenova. 1984; 70(5):712–721. (In Russ.).Zhang R, Taucer AI, Gashev AA, Muthuchamy M, Zawieja DC, Davis MJ. Maximum shortening velocity of lymphatic muscle approaches that of striated muscle. Am J Physiol Heart Circ Physiol. 2013;305(10):H1494–1507. Doi: 10.1152/ajpheart.00898.2012.Zhang R, Taucer AI, Gashev AA, Muthuchamy M, Zawieja DC, Davis MJ. Maximum shortening velocity of lymphatic muscle approaches that of striated muscle. Am J Physiol Heart Circ Physiol. 2013;305(10):H1494–1507. Doi: 10.1152/ajpheart.00898.2012.Muthuchamy M, Zawieja D. Molecular regulation of lymphatic contractility. Ann N Y Acad Sci. 2008;1131:89–99. Doi: 10.1196/annals.1413.008.Muthuchamy M, Zawieja D. Molecular regulation of lymphatic contractility. Ann N Y Acad Sci. 2008;1131:89–99. Doi: 10.1196/annals.1413.008.von der Weid PY, Crowe MJ, Van Helden DF. Endothelium-dependent modulation of pacemaking in lymphatic vessels of the guinea-pig mesentery. J Physiol. 1996;493(Pt 2):563–575. Doi: 10.1113/jphysiol.1996.sp021404.von der Weid PY, Crowe MJ, Van Helden DF. Endothelium-dependent modulation of pacemaking in lymphatic vessels of the guinea-pig mesentery. J Physiol. 1996;493(Pt 2):563–575. Doi: 10.1113/jphysiol.1996.sp021404.von der Weid PY, Rahman M, Imtiaz MS, van Helden DF. Spontaneous transient depolarizations in lymphatic vessels of the guinea pig mesentery: pharmacology and implication for spontaneous contractility. Am J Physiol Heart Circ Physiol. 2008;295(5):H1989–2000. Doi: 10.1152/ajpheart.00007.2008.von der Weid PY, Rahman M, Imtiaz MS, van Helden DF. Spontaneous transient depolarizations in lymphatic vessels of the guinea pig mesentery: pharmacology and implication for spontaneous contractility. Am J Physiol Heart Circ Physiol. 2008;295(5):H1989–2000. Doi: 10.1152/ajpheart.00007.2008.Лобов Г. И. Электрофизиологические свойства мембраны гладкомышечных клеток лимфатических сосудов быка // Журн. эволюционной биохимии и физиологии. – 1985. – № 3. – С. 271–276.Lobov GI. Electrophysiological properties of the membrane of smooth muscle cells from bovine lymphatic vessels. Zhurnal evolyutsionnoi biokhimii i fiziologii. 1985;21(3):271–276. (In Russ.).Лобов Г. И. Локализация и свойства пейсмекерных клеток лимфангиона // Докл. Акад. наук. – 1987. – Vol. 294, № 2. – С. 353–359.Lobov GI. Location and properties of the pacemaker cells of the lymphangion. Doklady Biological Sciences. 1987;294(2):353–359. (In Russ.).Mizuno R, Koller A, Kaley G. Regulation of the vasomotor activity of lymph microvessels by nitric oxide and prostaglandins. Am J Physiol. 1998;274(3):R790–R696. Doi: 10.1152/ajpregu.1998.274.3.R790.Mizuno R, Koller A, Kaley G. Regulation of the vasomotor activity of lymph microvessels by nitric oxide and prostaglandins. Am J Physiol. 1998;274(3):R790–R696. Doi: 10.1152/ajpregu.1998.274.3.R790.Wong BW, Zecchin A, García-Caballero M, Carmeliet P. Emerging Concepts in Organ-Specific Lymphatic Vessels and Metabolic Regulation of Lymphatic Development. Dev Cell. 2018;45(3):289–301. Doi: 10.1016/j.devcel.2018.03.021.Wong BW, Zecchin A, García-Caballero M, Carmeliet P. Emerging Concepts in Organ-Specific Lymphatic Vessels and Metabolic Regulation of Lymphatic Development. Dev Cell. 2018;45(3):289–301. Doi: 10.1016/j.devcel.2018.03.021.von der Weid PY. Lymphatic Vessel Pumping. Adv Exp Med Biol. 2019;1124:357–377. Doi: 10.1007/978-981-135895-1_15.von der Weid PY. Lymphatic Vessel Pumping. Adv Exp Med Biol. 2019;1124:357–377. Doi: 10.1007/978-981-135895-1_15.Koller A, Mizuno R, Kaley G. Flow reduces the amplitude and increases the frequency of lymphatic vasomotion: role of endothelial prostanoids. Am J Physiol. 1999;277(6):R16831689. Doi: 10.1152/ajpregu.1999.277.6.R1683.Koller A, Mizuno R, Kaley G. Flow reduces the amplitude and increases the frequency of lymphatic vasomotion: role of endothelial prostanoids. Am J Physiol. 1999;277(6):R16831689. Doi: 10.1152/ajpregu.1999.277.6.R1683.Leak LV, Cadet JL, Griffin CP, Richardson K. Nitric oxide production by lymphatic endothelial cells in vitro. Biochem Biophys Res Commun. 1995;217(1):96–105. Doi: 10.1006/bbrc.1995.2750.Leak LV, Cadet JL, Griffin CP, Richardson K. Nitric oxide production by lymphatic endothelial cells in vitro. Biochem Biophys Res Commun. 1995;217(1):96–105. Doi: 10.1006/bbrc.1995.2750.von der Weid PY, Crowe MJ, van Helden DF. Endothelium-dependent modulation of pacemaking in lymphatic vessels of the guinea-pig mesentery. J Physiol. 1996;493(Pt 2):563–575. Doi: 10.1113/jphysiol.1996.sp021404.von der Weid PY, Crowe MJ, van Helden DF. Endothelium-dependent modulation of pacemaking in lymphatic vessels of the guinea-pig mesentery. J Physiol. 1996;493(Pt 2):563–575. Doi: 10.1113/jphysiol.1996.sp021404.Rehal S, von der Weid PY. Experimental ileitis alters prostaglandin biosynthesis in mesenteric lymphatic and blood vessels. Prostaglandins Other Lipid Mediat. 2015;116117:37–48. Doi: 10.1016/j.prostaglandins.2014.11.001.Rehal S, von der Weid PY. Experimental ileitis alters prostaglandin biosynthesis in mesenteric lymphatic and blood vessels. Prostaglandins Other Lipid Mediat. 2015;116117:37–48. Doi: 10.1016/j.prostaglandins.2014.11.001.Lobov GI, Dvoretskii DP. Endothelium-dependent hyperpolarization–mediated relaxation pathway in bovine mesenteric lymph nodes. Doklady Biological Sciences. 2019; 484(1):10–12.Lobov GI, Dvoretskii DP. Endothelium-dependent hyperpolarization–mediated relaxation pathway in bovine mesenteric lymph nodes. Doklady Biological Sciences. 2019; 484(1):10–12.Лобов Г. И. Роль сероводорода в дилатации брыжеечных лимфатических сосудов быка. Бюл. эксперим. биологии и медицины. – 2020. – Т. 169, № 3. – С. 272–276.Lobov GI. The role of hydrogen sulfide in the dilatation of the bovine mesenteric lymphatic vessels. Bulletin of Experimental Biology and Medicine. 2020;169(3):272–276. (In Russ.).Unt DV, Lobov GI. Inhibitory effect of interferons on contractive activity of bovine mesenteric lymphatic vessels and nodes. Bulletin of Experimental Biology and Medicine. 2017;164(2):123–126.Unt DV, Lobov GI. Inhibitory effect of interferons on contractive activity of bovine mesenteric lymphatic vessels and nodes. Bulletin of Experimental Biology and Medicine. 2017;164(2):123–126.Лобов Г. И., Панькова М. Н., Абдрешов С. Н. Фазные и тонические сокращения лимфатических сосудов и узлов при действии предсердного натрийуретического пептида // Регионар. кровообращение и микроциркуляция. – 2015. – Т. 14, № 3. – С. 72–77. Doi: 10.24884/1682-66552015-14-3-72-77.Lobov GI, Pankova MN, Abdreshov SN. Phase and tonic contractions of the lymphatic vessels and nodes under the action of the atrial natriuretic peptide. Regionarnoe krovoobrashchenie i mikrotsirkulyatsiya. 2015;14(3):72–77. (In Russ.). Doi: 10.24884/1682-66552015-14-3-72-77.Lobov GI, Unt DV. Protective effect of dexamethasone on lipopolysaccharide-induced inhibition of contractile function of isolated lymphatic vessels and nodes. Bulletin of Experimental Biology and Medicine. 2018;165(5):602–605. Doi: 10.1007/s10517-018-4222-7.Lobov GI, Unt DV. Protective effect of dexamethasone on lipopolysaccharide-induced inhibition of contractile function of isolated lymphatic vessels and nodes. Bulletin of Experimental Biology and Medicine. 2018;165(5):602–605. Doi: 10.1007/s10517-018-4222-7.D’Andrea V, Panarese A, Taurone S, Coppola L, Cavallotti C, Artico M. Human lymphatic mesenteric vessels: morphology and possible function of aminergic and NPY-ergic nerve fibers. Lymphat. Res Biol. 2015;13(3):170–175. Doi: 10.1089/lrb.2015.0018.D’Andrea V, Panarese A, Taurone S, Coppola L, Cavallotti C, Artico M. Human lymphatic mesenteric vessels: morphology and possible function of aminergic and NPY-ergic nerve fibers. Lymphat. Res Biol. 2015;13(3):170–175. Doi: 10.1089/lrb.2015.0018.Telinius N, Baandrup U, Rumessen J, Pilegaard H, Hjortdal V, Aalkjaer C, Boedtkjer DB. The human thoracic duct is functionally innervated by adrenergic nerves. Am J Physiol Heart Circ Physiol. 2014;15;306(2):H206–213. Doi: 10.1152/ajpheart.00517.2013.Telinius N, Baandrup U, Rumessen J, Pilegaard H, Hjortdal V, Aalkjaer C, Boedtkjer DB. The human thoracic duct is functionally innervated by adrenergic nerves. Am J Physiol Heart Circ Physiol. 2014;15;306(2):H206–213. Doi: 10.1152/ajpheart.00517.2013.Hashimoto S, Kawai Y, Ohhashi T. Effects of vasoactive substances on the pig isolated hepatic lymph vessels. J Pharmacol Exp Ther. 1994;269(2):482–488.Hashimoto S, Kawai Y, Ohhashi T. Effects of vasoactive substances on the pig isolated hepatic lymph vessels. J Pharmacol Exp Ther. 1994;269(2):482–488.Ohtani O, Ohtani Y. Structure and function of rat lymph nodes. Arch Histol Cytol. 2008;71(2):69–76. Doi: 10.1679/aohc.71.69.Ohtani O, Ohtani Y. Structure and function of rat lymph nodes. Arch Histol Cytol. 2008;71(2):69–76. Doi: 10.1679/aohc.71.69.Louie DAP, Liao S. Lymph Node Subcapsular Sinus Macrophages as the Frontline of Lymphatic Immune Defense. Front Immunol. 2019;10:347. Doi: 10.3389/fimmu.2019.00347.Louie DAP, Liao S. Lymph Node Subcapsular Sinus Macrophages as the Frontline of Lymphatic Immune Defense. Front Immunol. 2019;10:347. Doi: 10.3389/fimmu.2019.00347.Angel CE, Chen CJ, Horlacher OC, Winkler S, John T, Browning J, MacGregor D, Cebon J, Dunbar PR. Distinctive localization of antigen-presenting cells in human lymph nodes. Blood. 2009 Feb 5;113(6):1257–1267.Angel CE, Chen CJ, Horlacher OC, Winkler S, John T, Browning J, MacGregor D, Cebon J, Dunbar PR. Distinctive localization of antigen-presenting cells in human lymph nodes. Blood. 2009 Feb 5;113(6):1257–1267.Thornbury KD, McHale NG, Allen JM, Hughes G. Nerve-mediated contractions of sheep mesenteric lymph node capsules. J Physiol. 1990 Mar;422:513–522. Doi: 10.1113/jphysiol.1990.sp017998.Thornbury KD, McHale NG, Allen JM, Hughes G. Nerve-mediated contractions of sheep mesenteric lymph node capsules. J Physiol. 1990 Mar;422:513–522. Doi: 10.1113/jphysiol.1990.sp017998.Hughes GA, Allen JM. Neural modulation of bovine mesenteric lymph node contraction. Exp Physiol. 1993;78(5):663–674. Doi: 10.1113/expphysiol.1993.sp003714.Hughes GA, Allen JM. Neural modulation of bovine mesenteric lymph node contraction. Exp Physiol. 1993;78(5):663–674. Doi: 10.1113/expphysiol.1993.sp003714.Lobov GI, Pankova MN. Mechanical properties of lymph node capsule. Bull Exp Biol Med. 2011;151(1):5–8. Doi: 10.1007/s10517-011-1246-7.Lobov GI, Pankova MN. Mechanical properties of lymph node capsule. Bull Exp Biol Med. 2011;151(1):5–8. Doi: 10.1007/s10517-011-1246-7.Лобов Г. И., Панькова М. Н. NO-зависимая модуляция сократительной функции гладких мышц капсулы лимфатических узлов // Рос. физиол. журн. им. И. М. Сеченова. – 2010. – Т. 96, № 5. – С. 489–497.Lobov GI, Pan’kova MN. NO-dependent Modulation of Contractile Function in Capsule of Lymph Nodes. Rossiiskii fiziologicheskii zhurnal im. I. M. Sechenova. 2010;96(5):489–497. (In Russ.).Лобов Г. И., Унт Д. В. Дексаметазон предотвращает сепсис-индуцированное угнетение сократительной функции лимфатических сосудов и узлов посредством ингибирования индуцибельной NO-синтазы и циклооксигеназы-2 // Рос. физиол. журн. им. И. М. Сеченова. –2019. Т. 105, № 1. – С. 76–88.Lobov GI, Unt DV. Dexamethasone prevents sepsis-induced inhibition of the contractile function of the lymphatic vessels and nodes by inhibiting inducible NO synthase and cyclooxygenase-2. Rossiiskii fiziologicheskii zhurnal im. I. M. Sechenova. 2019;105(1):76–88. (In Russ.).Pan’kova MN, Lobov GI. Effect of heparin on contractile activity of lymph node capsule. Bull. Exp. Biol. Med. 2015;159(5):632–634.Pan’kova MN, Lobov GI. Effect of heparin on contractile activity of lymph node capsule. Bull. Exp. Biol. Med. 2015;159(5):632–634.Acton SE, Reis Е Sousa C. Dendritic cells in remodeling of lymph nodes during immune responses. Immunol Rev. 2016;271(1):221–229. Doi: 10.1111/imr.12414.Acton SE, Reis Е Sousa C. Dendritic cells in remodeling of lymph nodes during immune responses. Immunol Rev. 2016;271(1):221–229. Doi: 10.1111/imr.12414.Holdsworth SR, Gan PY. Cytokines: Names and Numbers You Should Care About. Clin J Am Soc Nephrol. 2015;10(12):2243–2254. Doi: 10.2215/CJN.07590714.Holdsworth SR, Gan PY. Cytokines: Names and Numbers You Should Care About. Clin J Am Soc Nephrol. 2015;10(12):2243–2254. Doi: 10.2215/CJN.07590714.Dayan JH, Ly CL, Kataru RP, Mehrara BJ. Lymphedema: Pathogenesis and Novel Therapies. Annu Rev Med. 2018 Jan 29;69:263–276. Doi: 10.1146/annurev-med-060116-022900.Dayan JH, Ly CL, Kataru RP, Mehrara BJ. Lymphedema: Pathogenesis and Novel Therapies. Annu Rev Med. 2018 Jan 29;69:263–276. Doi: 10.1146/annurev-med-060116-022900.von der Weid P-Y. Lymphatic Vessel Pumping. Adv Exp Med Biol. 2019;1124:357–377. Doi: 10.1007/978-98113-5895-1_15.von der Weid P-Y. Lymphatic Vessel Pumping. Adv Exp Med Biol. 2019;1124:357–377. Doi: 10.1007/978-98113-5895-1_15.von der Weid PY. Review article: lymphatic vessel pumping and inflammation – the role of spontaneous constrictions and underlying electrical pacemaker potentials. Aliment Pharmacol Ther. 200115(8):1115–1129. Doi: 10.1046/j.13652036.2001.01037.x.von der Weid PY. Review article: lymphatic vessel pumping and inflammation – the role of spontaneous constrictions and underlying electrical pacemaker potentials. Aliment Pharmacol Ther. 200115(8):1115–1129. Doi: 10.1046/j.13652036.2001.01037.x.Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, Ruddle NH, Jain RK, Fukumura D, Padera TP. Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci U S A. 2011;108(46):1878418789. Doi: 10.1073/pnas.1116152108.Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, Ruddle NH, Jain RK, Fukumura D, Padera TP. Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci U S A. 2011;108(46):1878418789. Doi: 10.1073/pnas.1116152108.von der Weid PY, Muthuchamy M. Regulatory mechanisms in lymphatic vessel contraction under normal and inflammatory conditions. Pathophysiology. 2010;17(4):263–276. Doi: 10.1016/j.pathophys.2009.10.005.von der Weid PY, Muthuchamy M. Regulatory mechanisms in lymphatic vessel contraction under normal and inflammatory conditions. Pathophysiology. 2010;17(4):263–276. Doi: 10.1016/j.pathophys.2009.10.005.Aldrich MB, Sevick-Muraca EM. Cytokines are systemic effectors of lymphatic function in acute inflammation. Cytokine. 2013;64(1):362–369. Doi: 10.1016/j.cyto.2013.05.015.Aldrich MB, Sevick-Muraca EM. Cytokines are systemic effectors of lymphatic function in acute inflammation. Cytokine. 2013;64(1):362–369. Doi: 10.1016/j.cyto.2013.05.015.Chen Y, Rehal S, Roizes S, Zhu HL, Cole WC, von der Weid PY. The pro-inflammatory cytokine TNF-alpha inhibits lymphatic pumping via activation of the NF-kappaB-iNOS signaling pathway. Microcirculation. 2017;24(3):10.1111/ micc.12364. Doi: 10.1111/micc.12364.Chen Y, Rehal S, Roizes S, Zhu HL, Cole WC, von der Weid PY. The pro-inflammatory cytokine TNF-alpha inhibits lymphatic pumping via activation of the NF-kappaB-iNOS signaling pathway. Microcirculation. 2017;24(3):10.1111/ micc.12364. Doi: 10.1111/micc.12364.Schwager S, Detmar M. Inflammation and Lymphatic Function. Front Immunol. 2019;26(10):308. Doi: 10.3389/fimmu.2019.00308.Schwager S, Detmar M. Inflammation and Lymphatic Function. Front Immunol. 2019;26(10):308. Doi: 10.3389/fimmu.2019.00308.Breslin JW, Yang Y, Scallan JP, Sweat RS, Adderley SP, Murfee WL. Lymphatic Vessel Network Structure and Physiology. Compr Physiol. 2018;9(1):207–299. Doi: 10.1002/cphy.c180015.Breslin JW, Yang Y, Scallan JP, Sweat RS, Adderley SP, Murfee WL. Lymphatic Vessel Network Structure and Physiology. Compr Physiol. 2018;9(1):207–299. Doi: 10.1002/cphy.c180015.

The authors declare that there are no conflicts of interest present.