Abstract
The lymphatic system is an elaborate network of vessels that act harmoniously to pump fluid and cells, collectively called lymph, from the interstitial space into the blood circulation. The journey of lymph begins with the extravasation of fluid and cells from the blood capillaries into the interstitium. These are then taken up by the initial lymphatic vessels and are termed lymph. The initial lymphatic vessels have unique button-like junctions that form structures called «primary lymphatic valves» which allow unidirectional flow of interstitial fluid into the initial lymphatics. The fluid is then drained into the pre-collecting and the collecting lymphatic vessels. Bileaflet valves, found throughout the collecting lymphatic vessels, prevent the backflow of lymph and segment the vessels into discrete sections known as lymphangions. Lymphangions act as discretized pumps due to their ability to rapidly and phasically contract their walls through the action of lymphatic muscle cells, propelling lymph downstream. Collecting vessels connect to lymph nodes where lymph is filtered. A small fraction of entering lymph flows deeper into the lymph node and enters the blood circulation through lymph node venules. The majority of lymph flows into efferent lymphatics and is eventually merging into the thoracic duct and is deposited into the subclavian vein after passing through a final lymphovenous valve.
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Highlighted References
Baluk P, Fuxe J, Hashizume H, Romano T, Lashnits E, Butz S, et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med [Internet]. 2007;204(10):2349–62. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2118470&tool=pmcentrez&rendertype=abstract.
Muthuchamy M, Gashev A, Boswell N. Molecular and functional analyses of the contractile apparatus in lymphatic muscle. FASEB J. 2003;17(8):920–2.
Davis MJ, Rahbar E, Gashev AA, Zawieja DC, Moore JE. Determinants of valve gating in collecting lymphatic vessels from rat mesentery. Am J Physiol Heart Circ Physiol. 2011;301(1):48–60.
Dixon JB, Greiner ST, Gashev AA, Cote GL, Moore JE, Zawieja DC. Lymph flow, shear stress, and lymphocyte velocity in rat mesenteric prenodal lymphatics. Microcirculation. 2006;13(7):597–610.
Schmid-Schonbein GW. Microlymphatics and lymph flow. Physiol Rev. 1990;70(4):987 LP–1028.
References
Swartz MA. The physiology of the lymphatic system. Adv Drug Deliv Rev. 2001;50(1–2):3–20.
Granger HJ. Role of the interstitial matrix and lymphatic pump in regulation of transcapillary fluid balance. Microvasc Res. 1979;18(2):209–16.
Levick JR. Flow through interstitium and other fibrous matrices. Q J Exp Physiol [Internet]. 1987;72(4):409–37. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3321140.
Aukland K, Reed RK. Interstitial-lymphatic mechanisms in the control of extracellular fluid volume. Physiol Rev [Internet]. 1993;73(1):1 LP–78. Available from: http://physrev.physiology.org/content/73/1/1.abstract.
Olszewski WL. The lymphatic system in body homeostasis. Lymphat Res Biol. 2003;1(1):11–21.
Yoffey JM, Courtice FC. Lymphatics, lymph and the lymphomyeloid complex [Internet]. Academic Press. 1970. Available from: https://books.google.com/books?id=ROVqAAAAMAAJ.
Nipper ME, Dixon JB. Engineering the lymphatic system. Cardiovasc Eng Technol [Internet]. 2011;2(4):296–308. Available from: http://dx.doi.org/10.1007/s13239-011-0054-6.
Swartz MA, Kaipainen A, Netti P, Brekken C, Boucher Y, Grodzinsky A, et al. Mechanics of interstitial-lymphatic fluid transport: theoretical foundation and experimental validation. J Biomech. 1999;32(12):1297–307.
Leak L. Electron microscopic observations on lymphatic capillaries and the structural components of the connective tissue-lymph interface. Microvasc Res. 1970;2(4):361–91.
Bazigou E, Wilson JT, Moore JE. Primary and secondary lymphatic valve development: molecular, functional and mechanical insights. Microvasc Res. 2014;96(5):38–45.
Leak LV, Burke JF. Fine structure of the lymphatic capillary and the adjoining connective tissue area. Am J Anat United States. 1966;118(3):785–809.
Leak LV, Burke JF. Electron microscopic study of lymphatic capillaries in the removal of connective tissue fluids and particulate substances. Lymphology United States. 1968;1(2):39–52.
Trzewik J, Mallipattu SK, Artmann GM, Delano FA, Schmid-Schonbein GW. Evidence for a second valve system in lymphatics: endothelial microvalves. FASEB J Off Publ Fed Am Soc Exp Biol United States. 2001 Aug;15(10):1711–7.
Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB, Achen MG. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer [Internet] Nature Publishing Group. 2014;14(3):159–72. Available from: http://www.nature.com/doifinder/10.1038/nrc3677.
Gashev AA. Physiological aspects of lymphatic contractile function. Ann N Y Acad Sci. 2002;979:178–87.
Schmid-Schonbein GW. Mechanisms causing initial lymphatics to expand and compress to promote lymph flow. Arch Histol Cytol Japan. 1990;53(Suppl):107–14.
Casley-Smith JR. Are the initial lymphatics normally pulled open by the anchoring filaments? Lymphology [Internet]. 1980;13(3):120–9. Available from: http://europepmc.org/abstract/MED/7442305.
Negrini D, Moriondo A. Lymphatic anatomy and biomechanics. J Physiol. 2011;589(Pt 12):2927–34.
Triacca V, Guc E, Kilarski WW, Pisano M, Swartz MA. Transcellular pathways in lymphatic endothelial cells regulate changes in solute transport by fluid stress. Circ Res [Internet]. 2017. Available from: http://circres.ahajournals.org/content/early/2017/01/25/CIRCRESAHA.116.309828.abstract.
Kvietys PR, Granger DN. Role of intestinal lymphatics in interstitial volume regulation and transmucosal water transport. Ann N Y Acad Sci [Internet]. Blackwell Publishing Inc. 2010;1207:E29–43. Available from: http://dx.doi.org/10.1111/j.1749-6632.2010.05709.x.
Azzali G. The passage of macrophages and lymphocytes from the interstitium across the lymphatic endothelium of rat lacteals. Cell Tissue Res [Internet]. 1990;262(1):191–3. Available from: http://dx.doi.org/10.1007/BF00327761.
Randolph GJ, Miller NE. Lymphatic transport of high-density lipoproteins and chylomicrons. J Clin Invest [Internet] The American Society for Clinical Investigation. 2014;124(3):929–35. Available from: https://doi.org/10.1172/JCI71610.
Florence AT, Hussain N. Transcytosis of nanoparticle and dendrimer delivery systems: evolving vistas. Adv Drug Deliv Rev [Internet]. 2001;50(Supple):S69–89. Available from: www.sciencedirect.com/science/article/pii/S0169409X01001843.
Reed AL, Rowson SA, Dixon JB. Demonstration of ATP dependent, transcellular transport of lipid across the lymphatic endothelium using an in vitro model of the lacteal. Pharm Res [Internet]. 2013;30(12). doi:10.1007/s11095-013-1218-x. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849718/.
Dixon JB. Mechanisms of chylomicron uptake into lacteals. Ann N Y Acad Sci [Internet] Blackwell Publishing Inc. 2010;1207:E52–7. Available from: http://dx.doi.org/10.1111/j.1749-6632.2010.05716.x.
Lee JS. Tissue fluid pressure, lymph pressure, and fluid transport in rat intestinal villi. Microvasc Res. 1986;31(2):170–83.
Dixon JB. Lymphatic lipid transport: sewer or Subway? Trends Endocrinol Metab [Internet]. 2010;21(8):480–7. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914116/.
Dobbins WO. Intestinal mucosal lacteal in transport of macromolecules and chylomicrons. Am J Clin Nutr [Internet]. 1971;24(1):77–90. Available from: http://ajcn.nutrition.org/content/24/1/77.abstract.
Florey H. Observations on the contractility of lacteals. J Physiol [Internet]. 1927;62(3):267–72. Available from: http://dx.doi.org/10.1113/jphysiol.1927.sp002357.
Florey H. Observations on the contractility of lacteals: part II. J Physiol [Internet]. 1927;63(1):1–18. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1514918/.
Choe K, Jang JY, Park I, Kim Y, Ahn S, Park DY, et al. Intravital imaging of intestinal lacteals unveils lipid drainage through contractility. J Clin Invest. 2015;125(11):4042–52.
Tso P, Pitts V, Granger D. Role of lymph flow in intestinal chylomicron transport. Am J Phys. 1985;249(1):G21–8.
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):1224–35.
Nurmi H, Saharinen P, Zarkada G, Zheng W, Robciuc MR, Alitalo K. VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption. EMBO Mol Med [Internet]. 2015. Available from: http://embomolmed.embopress.org/content/early/2015/10/09/emmm.201505731.abstract.
Lynch PM, Delano FA, Schmid-Schonbein GW. The primary valves in the initial lymphatics during inflammation. Lymphat Res Biol [Internet]. 2007;5(1):3–10. Available from: www.ncbi.nlm.nih.gov/pubmed/17508898%5Cnhttp://online.liebertpub.com/doi/pdfplus/10.1089/lrb.2007.5102.
Russo E, Teijeira A, Vaahtomeri K, Willrodt A-H, Bloch JS, Nitschké M, et al. Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels. Cell Rep [Internet] Elsevier. 2017;14(7):1723–34. Available from: http://dx.doi.org/10.1016/j.celrep.2016.01.048.
Weber M, Hauschild R, Schwarz J, Moussion C, de Vries I, Legler DF, et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science [Internet]. 2013;339(6117):328 LP–332. Available from: http://science.sciencemag.org/content/339/6117/328.abstract.
Miteva DO, Rutkowski JM, Dixon JB, Kilarski W, Shields JD, Swartz MA. Transmural flow modulates cell and fluid transport functions of lymphatic endothelium. Circ Res [Internet]. 2010;106(5):920 LP–931. Available from: http://circres.ahajournals.org/content/106/5/920.abstract.
Johnson LA, Clasper S, Holt AP, Lalor PF, Baban D, Jackson DG. An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium. J Exp Med [Internet]. 2006;203(12):2763–77. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2118156&tool=pmcentrez&rendertype=abstract.
Zampell JC, Aschen S, Weitman ES, Yan A, Elhadad S, De Brot AM, et al. Regulation of adipogenesis by lymphatic fluid stasis part I: adipogenesis, fibrosis, and inflammation. Plast Reconstr Surg [Internet]. 2012;129(4):825–34. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433726/.
Rockson SG. The lymphatics and the inflammatory response: lessons learned from human lymphedema. Lymphat Res Biol. 2013;11(3):117–20. Available from: http://dx.doi.org/10.1089/lrb.2013.1132.
Von Der Weid PY. Review article: lymphatic vessel pumping and inflammation – the role of spontaneous constrictions and underlying electrical pacemaker potentials. Aliment Pharmacol Ther. 2001;15(8):1115–29.
Lynch LL, Mendez U, Waller AB, Gillette AA, Guillory RJ, Goldman J. Fibrosis worsens chronic lymphedema in rodent tissues. Am J Physiol Heart Circ Physiol. 2015;308(10):H1229–36.
Olszewski WL, Jain P, Ambujam G, Zaleska M, Cakala M, Gradalski T. Tissue fluid pressure and flow during pneumatic compression in lymphedema of lower limbs. Lymphat Res Biol. 2011;9(2):77–83.
Kim H, Kataru RP, Koh GY. Inflammation-associated lymphangiogenesis: a double-edged sword? J Clin Invest [Internet] (The American Society for Clinical Investigation). 2014;124(3):936–42. Available from: https://doi.org/10.1172/JCI71607.
Ogata F, Fujiu K, Matsumoto S, Nakayama Y, Shibata M, Oike Y, et al. Excess Lymphangiogenesis cooperatively induced by macrophages and CD4+ T cells drives the pathogenesis of lymphedema. J Invest Dermatol [Internet]. 2016;136(3):706–14. Available from: www.sciencedirect.com/science/article/pii/S0022202X15000925.
Alitalo K, Tammela T, Petrova TV. Lymphangiogenesis in development and human disease. Nature [Internet]. 2005;438(7070):946–53. Available from: http://dx.doi.org/10.1038/nature04480.
Karkkainen MJ, Ferrell RE, Lawrence EC, Kimak MA, Levinson KL, McTigue MA, et al. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet [Internet]. 2000;25(2):153–9. Available from: http://dx.doi.org/10.1038/75997.
Makinen T, Jussila L, Veikkola T, Karpanen T, Kettunen MI, Pulkkanen KJ, et al. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat Med [Internet]. 2001;7(2):199–205. Available from: http://dx.doi.org/10.1038/84651.
Jeltsch M, Tammela T, Alitalo K, Wilting J. Genesis and pathogenesis of lymphatic vessels. Cell Tissue Res [Internet]. 2003;314(1):69–84. Available from: http://dx.doi.org/10.1007/s00441-003-0777-2.
Saito Y, Nakagami H, Kaneda Y, Morishita R. Lymphedema and therapeutic lymphangiogenesis. Biomed Res Int. 2013;2013:804675.
Rutkowski JM, Moya M, Johannes J, Goldman J, Swartz MA. Secondary lymphedema in the mouse tail: lymphatic hyperplasia, VEGF-C upregulation, and the protective role of MMP-9. Microvasc Res [Internet]. 2006;72(3):161–71. Available from: http://www.sciencedirect.com/science/article/pii/S0026286206000720.
Liao S, von der Weid P-Y. Inflammation-induced lymphangiogenesis and lymphatic dysfunction. Angiogenesis [Internet]. 2014;17(2):325–34. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981917/.
Scavelli C, Weber E, Aglianò M, Cirulli T, Nico B, Vacca A, et al. Lymphatics at the crossroads of angiogenesis and lymphangiogenesis. J Anat. 2004;204(6):433–49.
Sacchi G, Weber E, Agliano M, Raffaelli N, Comparini L. The structure of superficial lymphatics in the human thigh: precollectors. Anat Rec. 1997;247(1):53–62.
Albertine KH, Fox LM, O’Morchoe CCC. The morphology of canine lymphatic valves. Anat Rec. 1982;202(4):453–61.
Pan W-R, le Roux CM, Levy SM, Briggs CA. The morphology of the human lymphatic vessels in the head and neck. Clin Anat. 2010;23(March):654–61.
McHale NG, Roddie IC. The effect of transmural pressure on pumping activity in isolated bovine lymphatic vessels. J Physiol. 1976;261(2):255–69.
Geng X, Cha B, Mahamud MR, Lim KC, Silasi-Mansat R, Uddin MKM, et al. Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development. Dev Biol Elsevier. 2016;409(1):218–33.
Hess PR, Rawnsley DR, Jakus Z, Yang Y, Sweet DT, Fu J, et al. Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life. J Clin Invest. 2014;124(1):273–84.
Muthuchamy M, Zawieja D. Molecular regulation of lymphatic contractility. Ann N Y Acad Sci. 2008;1131:89–99.
Gashev AA, Davis MJ, Delp MD, Zawieja DC. Regional variations of contractile activity in isolated rat lymphatics. Microcirculation. 2004;11(6):477–92.
McHale NG, Roddie IC. Pumping activity in isolated segments of bovine mesenteric lymphatics. J Physiol. 1975;261(1):70–2.
Jamalian S, Davis MJ, Zawieja DC, Moore JE. Network scale modeling of lymph transport and its effective pumping parameters. PLoS One. 2016;11(2):1–18.
Davis MJ, Scallan JP, Wolpers JH, Muthuchamy M, Gashev AA, Zawieja DC. Intrinsic increase in lymphangion muscle contractility in response to elevated afterload. Am J Physiol Heart Circ Physiol. 2012;303(7):H795–808.
Zawieja DC, Davis KL, Schuster R, Hinds WM, Granger HJ. Distribution, propagation, and coordination of contractile activity in lymphatics. Am J Phys. 1993;264(4 Pt 2):H1283–91.
Eisenhoffer J, Kagal A, Klein T, Johnston MG. Importance of valves and lymphangion contractions in determining pressure gradients in isolated lymphatics exposed to elevations in outflow pressure. Microvasc Res. 1995;49:97–110.
Unno N, Nishiyama M, Suzuki M, Tanaka H, Yamamoto N, Sagara D, et al. A novel method of measuring human lymphatic pumping using indocyanine green fluorescence lymphography. J Vasc Surg Elsevier Inc. 2010;52(4):946–52.
Cintolesi V, Stanton AW, BCh M, Bains SK, Cousins E, Michael Peters A, et al. Constitutively enhanced lymphatic pumping in the upper limbs of women who later develop breast cancer-related lymphedema. Lymphat Res Biol. 2016;14(2):50–61.
Nelson TS, Akin RE, Weiler MJ, Kassis T, Kornuta JA, Dixon JB. Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging. Am J Physiol Regul Integr Comp Physiol. 2014;306(5):R281–90.
Von Der WP, Zawieja DC. Lymphatic smooth muscle: the motor unit of lymph drainage. Int J Biochem Cell Biol. 2004;36:1147–53.
Ohhashi T. The response of lymphatic smooth muscles to vasoactive substances. Pflugers Arch. 1986;c:341–7.
McHale N. Nervous control of the lymphatic system. Vasc Med Rev. 1993;4:307–19.
Amerini S, Ziche M, Greiner ST, Zawieja DC. Effects of substance P on mesenteric lymphatic contractility in the rat. Lymphat Res Biol. 2004;2(1):2–10.
Allen JM, McHale NG, Rooney BM. Effect of norepinephrine on contractility of isolated mesenteric lymphatics. Am J Physiol Heart Circ Physiol. 1983;244(4):H479 LP–H486.
Allen JM, Iggulden HL, McHale NG. Beta-adrenergic inhibition of bovine mesenteric lymphatics. J Physiol. 1986;374:401–11.
ALLEN JM, BURKE EP, JOHNSTON MG, NG MH. The inhibitory effect of aspirin on lymphatic contractility. Br J Pharmacol. 1984;82(2):509–14.
Allen JM, McHale NG. Neuromuscular transmission in bovine mesenteric lymphatics. Microvasc Res. 1986;31(1):77–83.
Scallan JP, Davis MJ, Huxley VH. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides. J Physiol. 2013;591(Pt 20):5071–81.
Ivanov S, Scallan JP, Kim KW, Werth K, Johnson MW, Saunders BT, et al. CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability. J Clin Invest. 2016;126(4):1581–91.
Kuan EL, Ivanov S, Bridenbaugh EA, Victora G, Wang W, Childs EW, et al. Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node–homing adipose tissue dendritic cells. J Immunol. 2015;194(11):5200–10.
Fonseca DMD, Hand TW, Han SJ, Gerner MY, Zaretsky AG, Byrd AL, et al. Microbiota-dependent Sequelae of acute infection compromise tissue-specific immunity. Cell Elsevier Inc. 2015;163(2):354–66.
Chatterjee V, Gashev AA. Aging-associated shifts in functional status of mast cells located by adult and aged mesenteric lymphatic vessels. AJP Hear Circ Physiol. 2012;303(6):H693–702.
Jawdat DM, Albert EJ, Rowden G, Haidl ID, Marshall JS. IgE-mediated mast cell activation induces Langerhans cell migration in vivo. J Immunol. 2004;173(8):5275–82.
Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, et al. Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci U S A. 2011;108(46):18784–9.
Gashev AA, Davis MJ, Zawieja DC. Inhibition of the active lymph pump by flow in rat mesenteric lymphatics and thoracic duct. J Physiol. 2002;540(Pt 3):1023–37.
von der Weid PY, Crowe MJ, Van Helden DF. Endothelium-dependent modulation of pacemaking in lymphatic vessels of the guinea-pig mesentery. J Physiol [Internet]. 1996;493(Pt 2):563–75. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1158938&tool=pmcentrez&rendertype=abstract.
Schmid-Schönbein GW. Nitric oxide (NO) side of lymphatic flow and immune surveillance. Proc Natl Acad Sci U S A. 2012;109(1):3–4.
Nizamutdinova IT, Maejima D, Nagai T, Bridenbaugh E, Thangaswamy S, Chatterjee V, et al. Involvement of histamine in endothelium-dependent relaxation of mesenteric lymphatic vessels. Microcirculation. 2014;21(7):640–8.
Kornuta JA, Nepiyushchikh Z, Gasheva OY, Mukherjee A, Zawieja DC, Dixon JB, et al. Effects of dynamic shear and transmural pressure on wall shear stress sensitivity in collecting lymphatic vessels. Am J Physiol Regul Integr Comp Physiol. 2015;309(9):R1122–34.
Kassis T, Yarlagadda SC, Kohan AB, Tso P, Breedveld V, Dixon JB. Post-prandial lymphatic pump function after a high-fat meal: a characterization of contractility, flow and viscosity. Am J Physiol Gastrointest Liver Physiol. 2016;310(10). doi:10.1152/ajpgi.00318.2015.
Jafarnejad M, Cromer WE, Kaunas RR, Zhang SL, Zawieja DC, Moore JE, et al. Measurement of shear stress-mediated intracellular calcium dynamics in human dermal lymphatic endothelial cells. Am J Physiol Heart Circ Physiol. 2015;308(7):H697–706.
Baeyens N, Nicoli S, Coon BG, Ross TD, Van Den Dries K, Han J, et al. Vascular remodeling is governed by a vegfr3-dependent fluid shear stress set point. elife. 2015;2015(4):1–35.
Munn LL. Mechanobiology of lymphatic contractions. Semin Cell Dev Biol Elsevier Ltd. 2015;38:67–74.
Telinius N, Drewsen N, Pilegaard H, Kold-Petersen H, de Leval M, Aalkjaer C, et al. Human thoracic duct in vitro: diameter-tension properties, spontaneous and evoked contractile activity. Am J Physiol Heart Circ Physiol. 2010;299(3):H811–8.
Gashev AA, Zhang RZ, Muthuchamy M, Zawieja DC, Davis MJ. Regional heterogeneity of length-tension relationships in rat lymph vessels. Lymphat Res Biol. 2012;10(1):14–9.
Gashev AA, Zawieja DC. Hydrodynamic regulation of lymphatic transport and the impact of aging. Pathophysiology [Internet] Elsevier Ireland Ltd. 2010;17(4):277–87. Available from: http://dx.doi.org/10.1016/j.pathophys.2009.09.002.
McHale NG, Thornbury K. A method for studying lymphatic pumping activity in conscious and anaesthetized sheep. J Physiol. 1986;378(1):109–18.
Mawhinney H, Roddie IC. Spontaneous activity in isolated bovine mesenteric lymphatics. J Physiol. 1973;229(2):339–48.
Cotton KD, Hollywood MA, McHale NG, Thornbury KD. Outward currents in smooth muscle cells isolated from sheep mesenteric lymphatics. J Physiol. 1997;503(1):1–11.
Beckett EAH, Hollywood MA, Thornbury KD, McHale NG. Spontaneous electrical activity in sheep mesenteric lymphatics. Lymphat Res Biol. 2007;5(1):29–43.
Imtiaz MS, Zhao J, Hosaka K, von der Weid P-Y, Crowe M, van Helden DF. Pacemaking through Ca2+ stores interacting as coupled oscillators via membrane depolarization. Biophys J [Internet]. Elsevier. 2007;92(11):3843–61. Available from: http://dx.doi.org/10.1529/biophysj.106.095687.
Telinius N, Majgaard J, Kim S, Katballe N, Pahle E, Nielsen J, et al. Voltage-gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels. J Physiol. 2015;593(14):3109–22.
Lee S, Roizes S, von der Weid P-Y. Distinct roles of L- and T-type voltage-dependent Ca 2+ channels in regulation of lymphatic vessel contractile activity. J Physiol. 2014;592(24):5409–27.
Von Der Weid P-Y, Lee S, Imtiaz MS, Zawieja DC, Davis MJ. Electrophysiological properties of rat mesenteric lymphatic vessels and their regulation by stretch. Lymphat Res Biol. 2014;12:66–75.
Van HD. Pacemaker potentials in lymphatic smooth muscle of the guinea-pig mesentery. J Physiol [Internet]. 1993;471:465–79. Available from: http://jp.physoc.org/content/471/1/465.short.
McCloskey KD, Toland HM, Hollywood MA, Thornbury KD, McHale NG. Hyperpolarisation-activated inward current in isolated sheep mesenteric lymphatic smooth muscle. J Physiol. 1999;521:Pt 1:201–11.
Briggs Boedtkjer D, Rumessen J, Baandrup U, Skov Mikkelsen M, Telinius N, Pilegaard H, et al. Identification of interstitial cajal-like cells in the human thoracic duct. Cells Tissues Organs. 2013;197(2):145–8.
McHale NG, Meharg MK. Co-ordination of pumping in isolated bovine lymphatic vessels. J Physiol. 1992;450:503–12.
Survivors B. Exercise and the lymphatic system. Sports Med. 2005;35(6):461–71.
Coates G, O’Brodovich H, Goeree G. Hindlimb and lung lymph flows during prolonged exercise. J Appl Physiol. 1993 Aug;75(2):633 LP–638.
Havas E, Parviainen T, Vuorela J, Toivanen J, Nikula T, Vihko V. Lymph flow dynamics in exercising human skeletal muscle as detected by scintography. J Physiol. 1997;504(1):233–9.
Sjӧberg T, Norgren L, Steen S. Contractility of human leg lymphatics during exercise. Pdf. Lymphology. 1989;22(4):186–93.
Olszewski WL, Engeset A. Intrinsic contractility of prenodal lymph vessels and lymph flow in human leg. Am J Physiol Heart Circ Physiol. 1980 Dec;239(6):H775 LP–H783.
Moriondo A, Solari E, Marcozzi C, Negrini D. Diaphragmatic lymphatic vessel behavior during local skeletal muscle contraction. Am J Physiol Heart Circ Physiol. 2015;308(3):pH193–205.
Gretener SB, Läuchli S, Leu AJ, Koppensteiner R, Franzeck UK. Effect of venous and lymphatic congestion on lymph capillary pressure of the skin in healthy volunteers and patients with lymph edema. J Vasc Res. 2000;37(1):61–7.
Olszewski WL, Jain P, Ambujam G, Zaleska M, Cakala M, Gradalski T. Tissue fluid pressure and flow in the subcutaneous tissue in lymphedema – hints for manual and pneumatic compression therapy. Phlebolymphology. 2010;17(3):144–50.
Ogata F, Fujiu K, Koshim I, Nagai R, Manabe I, Manabe I. Phenotypic modulation of smooth muscle cells in lymphedema. Br J Dermatol. 2013;172(5):1286–93.
Mihara M, Hara H, Hayashi Y, Narushima M, Yamamoto T, Todokoro T, et al. Pathological steps of cancer-related lymphedema: histological changes in the collecting lymphatic vessels after lymphadenectomy. PLoS One. 2012;7(7):1–10.
Caulk AW, Dixon JB, Gleason RL. A lumped parameter model of mechanically mediated acute and long-term adaptations of contractility and geometry in lymphatics for characterization of lymphedema. Biomech Model Mechanobiol. 2016;5(6):1601–18.
Dongaonkar RM, Nguyen TL, Quick CM, Hardy J, Laine GA, Wilson E, et al. Adaptation of mesenteric lymphatic vessels to prolongedchanges in transmural pressure. Am J Physiol Heart Circ Physiol. 2013;305(9):203–10.
Rahbar E, Akl T, Coté GL, Moore JE, Zawieja DC. Lymph transport in rat mesenteric lymphatics experiencing edemagenic stress. Microcirculation. 2014;21(5):359–67.
Bains SK, Stanton AWB, Cintolesi V, Ballinger J, Allen S, Zammit C, et al. A constitutional predisposition to breast cancer-related lymphoedema and effect of axillary lymph node surgery on forearm muscle lymph flow. Breast Elsevier Ltd. 2015;24(1):68–74.
Heath TJ, Kerlin RL, Spalding HJ. Afferent pathways of lymph flow within the popliteal node in sheep. J Anat. 1986;149:65–75.
Roozendaal R, Mempel TR, Pitcher LA, Santiago F, Verschoor A, Mebius RE, et al. Conduits mediate transport of low molecular weight antigen to lymph node follicles. Immunity. 2009;30(2):264–76.
Adair TH, Guyton AC. Modification of lymph by lymph nodes. II. Effect of increased lymph node venous blood pressure. Am J Physiol Heart Circ Physiol. 1983;245(4):H616 LP–H622.
Adair TH, Guyton AC. Modification of lymph by lymph nodes. III. Effect of increased lymph hydrostatic pressure. Am J Physiol Heart Circ Physiol. 1985;249(4):H777 LP–H782.
Jafarnejad M, Woodruff MC, Zawieja DC, Carroll MC, Moore JE. Modeling lymph flow and fluid exchange with blood vessels in lymph nodes. Lymphat Res Biol. 2015;13(4):234–47.
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Mukherjee, A., Hooks, J., Dixon, J.B. (2018). Physiology: Lymph Flow. In: Lee, BB., Rockson, S., Bergan, J. (eds) Lymphedema. Springer, Cham. https://doi.org/10.1007/978-3-319-52423-8_8
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