The Lymphatic Highway: How Lymphatics Drive Lung Health and Disease

Oliver G, Kipnis J, Randolph GJ, Harvey NL (2020) The lymphatic vasculature in the 21(st) century: novel functional roles in homeostasis and disease. Cell 182:270–296. https://doi.org/10.1016/j.cell.2020.06.039

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alitalo K (2011) The lymphatic vasculature in disease. Nat Med 17:1371–1380. https://doi.org/10.1038/nm.2545

Article  CAS  PubMed  Google Scholar 

Choi I, Lee S, Hong YK (2012) The new era of the lymphatic system: no longer secondary to the blood vascular system. Cold Spring Harb Perspect Med 2:a006445. https://doi.org/10.1101/cshperspect.a006445

Article  CAS  PubMed  PubMed Central  Google Scholar 

Breslin JW, Yang Y, Scallan JP, Sweat RS, Adderley SP, Murfee WL (2018) Lymphatic vessel network structure and physiology. Compr Physiol 9:207–299. https://doi.org/10.1002/cphy.c180015

Article  PubMed  PubMed Central  Google Scholar 

Hu Z, Zhao X, Wu Z, Qu B, Yuan M, Xing Y, Song Y, Wang Z (2024) Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets. Signal Transduct Target Ther. https://doi.org/10.1038/s41392-023-01723-x

Article  PubMed  PubMed Central  Google Scholar 

Stump B, Cui Y, Kidambi P, Lamattina AM, El-Chemaly S (2017) Lymphatic changes in respiratory diseases: more than just remodeling of the lung? Am J Respir Cell Mol Biol 57:272–279. https://doi.org/10.1165/rcmb.2016-0290TR

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maldonado-Zimbron VE, Hong J, Russell P, Trevaskis NL, Windsor JA, Phillips ARJ (2021) Methods for studying pulmonary lymphatics. Eur Respir J. https://doi.org/10.1183/13993003.04106-2020

Article  PubMed  Google Scholar 

Baluk P, McDonald DM (2008) Markers for microscopic imaging of lymphangiogenesis and angiogenesis. Ann N Y Acad Sci 1131:1–12. https://doi.org/10.1196/annals.1413.001

Article  PubMed  Google Scholar 

Trivedi A, Reed HO (2023) The lymphatic vasculature in lung function and respiratory disease. Front Med (Lausanne) 10:1118583. https://doi.org/10.3389/fmed.2023.1118583

Article  PubMed  Google Scholar 

Ducoli L, Detmar M (2021) Beyond PROX1: transcriptional, epigenetic, and noncoding RNA regulation of lymphatic identity and function. Dev Cell 56:406–426. https://doi.org/10.1016/j.devcel.2021.01.018

Article  CAS  PubMed  Google Scholar 

Wilting J, Papoutsi M, Christ B, Nicolaides KH, von Kaisenberg CS, Borges J, Stark GB, Alitalo K, Tomarev SI, Niemeyer C, Rossler J (2002) The transcription factor Prox1 is a marker for lymphatic endothelial cells in normal and diseased human tissues. FASEB J 16:1271–1273. https://doi.org/10.1096/fj.01-1010fje

Article  CAS  PubMed  Google Scholar 

Monaghan RM, Page DJ, Ostergaard P, Keavney BD (2021) The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases. Cardiovasc Res 117:1877–1890. https://doi.org/10.1093/cvr/cvaa291

Article  CAS  PubMed  Google Scholar 

Kannan S, Rutkowski JM (2024) VEGFR-3 signaling in macrophages: friend or foe in disease? Front Immunol 15:1349500. https://doi.org/10.3389/fimmu.2024.1349500

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jackson DG (2019) Hyaluronan in the lymphatics: The key role of the hyaluronan receptor LYVE-1 in leucocyte trafficking. Matrix Biol 78–79:219–235. https://doi.org/10.1016/j.matbio.2018.02.001

Article  CAS  PubMed  Google Scholar 

Gordon EJ, Gale NW, Harvey NL (2008) Expression of the hyaluronan receptor LYVE-1 is not restricted to the lymphatic vasculature; LYVE-1 is also expressed on embryonic blood vessels. Dev Dyn 237:1901–1909. https://doi.org/10.1002/dvdy.21605

Article  CAS  PubMed  Google Scholar 

Gibbings SL, Thomas SM, Atif SM, McCubbrey AL, Desch AN, Danhorn T, Leach SM, Bratton DL, Henson PM, Janssen WJ, Jakubzick CV (2017) Three unique interstitial macrophages in the Murine Lung at Steady State. Am J Respir Cell Mol Biol 57:66–76. https://doi.org/10.1165/rcmb.2016-0361OC

Article  CAS  PubMed  PubMed Central  Google Scholar 

Min KH, Park SJ, Lee KS, Hwang SH, Kim SR, Moon H, Han HJ, Chung MJ, Lee YC (2011) Clinical usefulness of D2–40 in non-small cell lung cancer. Lung 189:57–63. https://doi.org/10.1007/s00408-010-9268-x

Article  CAS  PubMed  Google Scholar 

Astarita JL, Acton SE, Turley SJ (2012) Podoplanin: emerging functions in development, the immune system, and cancer. Front Immunol 3:283. https://doi.org/10.3389/fimmu.2012.00283

Article  PubMed  PubMed Central  Google Scholar 

Beretta E, Romano F, Sancini G, Grotberg JB, Nieman GF, Miserocchi G (2021) Pulmonary interstitial matrix and lung fluid balance from normal to the acutely injured lung. Front Physiol 12:781874. https://doi.org/10.3389/fphys.2021.781874

Article  PubMed  PubMed Central  Google Scholar 

Reed HO, Wang L, Sonett J, Chen M, Yang J, Li L, Aradi P, Jakus Z, D’Armiento J, Hancock WW, Kahn ML (2019) Lymphatic impairment leads to pulmonary tertiary lymphoid organ formation and alveolar damage. J Clin Invest 129:2514–2526. https://doi.org/10.1172/JCI125044

Article  PubMed  PubMed Central  Google Scholar 

Zhang PH, Zhang WW, Wang SS, Wu CH, Ding YD, Wu XY, Smith FG, Hao Y, Jin SW (2024) Efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS. JCI Insight. https://doi.org/10.1172/jci.insight.173440

Article  PubMed  PubMed Central  Google Scholar 

Ural BB, Caron DP, Dogra P, Wells SB, Szabo PA, Granot T, Senda T, Poon MML, Lam N, Thapa P, Lee YS, Kubota M, Matsumoto R, Farber DL (2022) Inhaled particulate accumulation with age impairs immune function and architecture in human lung lymph nodes. Nat Med 28:2622–2632. https://doi.org/10.1038/s41591-022-02073-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alon R, Sportiello M, Kozlovski S, Kumar A, Reilly EC, Zarbock A, Garbi N, Topham DJ (2021) Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19. Nat Rev Immunol 21:49–64. https://doi.org/10.1038/s41577-020-00470-2

Article  CAS  PubMed  Google Scholar 

Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG, Hicklin DJ, Jeltsch M, Petrova TV, Pytowski B, Stacker SA, Yla-Herttuala S, Jackson DG, Alitalo K, McDonald DM (2005) Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest 115:247–257. https://doi.org/10.1172/JCI22037

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cui Y, Wilder J, Rietz C, Gigliotti A, Tang X, Shi Y, Guilmette R, Wang H, George G, Nilo de Magaldi E, Chu SG, Doyle-Eisele M, McDonald JD, Rosas IO, El-Chemaly S (2014) Radiation-induced impairment in lung lymphatic vasculature. Lymphat Res Biol 12:238–250. https://doi.org/10.1089/lrb.2014.0012

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sozio F, Rossi A, Weber E, Abraham DJ, Nicholson AG, Wells AU, Renzoni EA, Sestini P (2012) Morphometric analysis of intralobular, interlobular and pleural lymphatics in normal human lung. J Anat 220:396–404. https://doi.org/10.1111/j.1469-7580.2011.01473.x

Article  PubMed  PubMed Central  Google Scholar 

Weber E, Sozio F, Borghini A, Sestini P, Renzoni E (2018) Pulmonary lymphatic vessel morphology: a review. Ann Anat 218:110–117. https://doi.org/10.1016/j.aanat.2018.02.011

Article 

Comments (0)

No login
gif