Lymphatic endothelium explained

The lymphatic endothelium refers to a specialized subset of endothelial cells located in the sinus systems of draining lymph nodes. Specifically, these endothelial cells line the branched sinus systems formed by afferent lymphatic vessels, forming a single-cell layer which functions in a variety of critical physiological processes. These lymphatic endothelial cells contribute directly to immune function and response modulation, provide transport selectivity, and demonstrate orchestration of bidirectional signaling cascades. Additionally, lymphatic endothelial cells may be implicated in downstream immune cell development as well as lymphatic organogenesis. (Jalkanen, S., Salmi, M. 2020)^[1] Until recently, lymphatic endothelial cells have not been characterized to their optimal potential. This system is very important in the function of continuous removal of interstitial fluid and proteins, while also having a significant function of entry for leukocytes and tumor cells. This leads to further research that is being developed on the relationship between lymphatic endothelium and metastasis of tumor cells (Pepper, M. S., & Skobe, M. 27 October 2003).^[2] The lymphatic capillaries are described to be blind ended vessels (closed on one end), and they are made up of a single non-fenestrated layer of endothelial cells; The lymph capillaries function to aid in the uptake of fluids, macromolecules, and cells. Although they are generally similar to blood capillaries, the lymph capillaries have distinct structural differences. Lymph capillaries consist of a more wide and irregular lumen, and the endothelium in lymph capillaries is much thinner as well (S. Pepper, Skobe 2003). Their origin has been speculated to vary based on them being dependent on specific tissue environments, and powered by organ-specific signals.(L. Gutierrez-Miranda, K. Yaniv, 2020).^[3] A lymph capillary endothelial cell is distinct from other endothelial cells in that collagen fibers are directly attached to its plasma membrane.

Although lymphatics were first described by Hippocrates in 400 BC and rediscovered as "milky veins in the gut of a well fed dog" in the 17th century by Gasparo Aselli, they were ignored for centuries until in 1937 Howard Florey showed that lymphatics enlarge in inflammation. At this stage vascular and lymphatic endothelia were seen to be morphologically distinct and lymphatic vessels considered less important. Later it was discovered that VEGF-R3 and VEGF-C/VEGF-D were the key growth factors controlling lymphatic endothelial proliferation. Markers of lymphatic endolthelium were not discovered until relatively recently. These being LYVE-1 (Jackson et al., 1999)^[4] and podoplanin (Kerjaschki, 1999).^[5]

See also

• Lymphatic system
• Immune system

Further reading

• Jalkanen, S., Salmi, M . Lymphatic endothelial cells of the lymph node . Nature Reviews Immunology . 20. 9 . 566–578 . 2020 . 32094869 . 10.1038/s41577-020-0281-x . 211265611 .
• Jackson DG . The lymphatics revisited: new perspectives from the hyaluronan receptor LYVE-1 . Trends in Cardiovascular Medicine . 13 . 1 . 1–7 . 2003 . 12554094 . 10.1016/S1050-1738(02)00189-5 .
• Banerji S . LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan . Journal of Cell Biology . 144 . 4 . 789–801 . 1999 . 10037799 . 10.1083/jcb.144.4.789 . 2132933 . vanc . Ni J . Wang SX . 3 . Clasper . S . Su . J . Tammi . R . Jones . M . Jackson . DG .
• Cunnick GH, Jiang WG, Gomez KF, Mansel RE . Lymphangiogenesis quantification using quantitative PCR and breast cancer as a model . Biochemical and Biophysical Research Communications . 288 . 4 . 1043–1046 . 2001 . 11689016 . 10.1006/bbrc.2001.5869 .
• Mouta Carreira C . LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis . Cancer Research . 61 . 22 . 8079–84 . 2001 . 11719431 . vanc . Nasser SM . di Tomaso E . 3 . Padera . TP . Boucher . Y . Tomarev . SI . Jain . RK .
• Cursiefen C . Lymphatic vessels in vascularized human corneas: immunohistochemical investigation using LYVE-1 and podoplanin . Investigative Ophthalmology & Visual Science . 43 . 7 . 2127–35 . 2002 . 12091407 . vanc . Schlötzer-Schrehardt U . Küchle M . 3 . Sorokin . L . Breiteneder-Geleff . S . Alitalo . K . Jackson . D .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proceedings of the National Academy of Sciences, USA . 99 . 26 . 16899–16903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . vanc . Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . free .
• Huang SS . Cloning, expression, characterization, and role in autocrine cell growth of cell surface retention sequence binding protein-1 . Journal of Biological Chemistry . 278 . 44 . 43855–43869 . 2003 . 12912978 . 10.1074/jbc.M306411200 . vanc . Tang FM . Huang YH . 3 . Liu . IH . Hsu . SC . Chen . ST . Huang . JS . free.
• Clark HF . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Research . 13 . 10 . 2265–2270 . 2003 . 12975309 . 10.1101/gr.1293003 . 403697 . vanc . Gurney AL . Abaya E . 3 . Baker . K . Baldwin . D . Brush . J . Chen . J . Chow . B . Chu . C .
• Gerhard DS . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Research . 14 . 10B . 2121–2127 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . vanc . Wagner L . Feingold EA . 3 . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Otsuki T . Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries . DNA Research . 12 . 2 . 117–126 . 2007 . 16303743 . 10.1093/dnares/12.2.117 . vanc . Ota T . Nishikawa T . 3 . Hayashi . K . Suzuki . Y . Yamamoto . J . Wakamatsu . A . Kimura . K . Sakamoto . K . free .
• Liu T . Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry . Journal of Proteome Research . 4 . 6 . 2070–2080 . 2006 . 16335952 . 10.1021/pr0502065 . 1850943 . vanc . Qian WJ . Gritsenko MA . 3 . Camp . David G. . Monroe . Matthew E. . Moore . Ronald J. . Smith . Richard D. .
• Kimura K . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 . vanc . Wakamatsu A . Suzuki Y . 3 . Ota . T . Nishikawa . T . Yamashita . R . Yamamoto . J . Sekine . M . Tsuritani . K .
• Nguyen VA . Infantile hemangioma is a proliferation of LYVE-1-negative blood endothelial cells without lymphatic competence . Modern Pathology . 19 . 2 . 291–298 . 2006 . 16424896 . 10.1038/modpathol.3800537 . vanc . Kutzner H . Fürhapter C . 3 . Tzankov . Alexandar . Sepp . Norbert . free .
• Gu B . Expression of lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) in the human placenta . Lymphatic Research and Biology . 4 . 1 . 11–17 . 2007 . 16569201 . 10.1089/lrb.2006.4.11 . vanc . Alexander JS . Gu Y . 3 . Zhang . Yanping . Lewis . David F. . Wang . Yuping . 3072054 .
• Llovet JM . A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis . Gastroenterology . 131 . 6 . 1758–1767 . 2007 . 17087938 . 10.1053/j.gastro.2006.09.014 . vanc . Chen Y . Wurmbach E . 3 . Roayaie . Sasan . Fiel . M. Isabel . Schwartz . Myron . Thung . Swan N. . Khitrov . Gregory . Zhang . Weijia . free .

Notes and References

1. Jalkanen . Sirpa . Salmi . Markko . Lymphatic endothelial cells of the lymph node . Nature Reviews Immunology. 24 February 2020 . 20 . 9 . 566–578 . 10.1038/s41577-020-0281-x . 32094869 . 211265611 . 15 November 2023.
2. The Journal of Cell Biology. 27 October 2003. 163 . 2 . 209–213 . 10.1083/jcb.200308082 . 14581448 . 2173536 . Lymphatic endothelium . Pepper . Michael S. . Skobe . Mihaela .
3. Gutierrez-Miranda . Laura . Karina . Yaniv . Cellular Origins of the Lymphatic Endothelium: Implications for Cancer Lymphangiogenesis . Frontiers in Physiology. 24 September 2020 . 11 . ePub . 10.3389/fphys.2020.577584 . 33071831 . 7541848 . free .
4. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan 1. The Journal of Cell Biology. 144. 4. 789–801. 10.1083/jcb.144.4.789. 1999. Banerji. Suneale. Ni. Jian. Wang. Shu-Xia. Clasper. Steven. Su. Jeffrey. Tammi. Raija. Jones. Margaret. Jackson. David G.. 10037799. 2132933.
5. Silvana. Breiteneder-Geleff. Afschin. Soleiman. Heinrich. Kowalski. Reinhard. Horvat. Gabriele. Amann. Ernst. Kriehuber. Katja. Diem. Wolfgang. Weninger. Erwin. Tschachler. Kari. Alitalo. Dontscho. Kerjaschki. Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic andothelium. American Journal of Pathology. 1999. 154. 2. 385–394. 10027397. 1849992. 10.1016/S0002-9440(10)65285-6.