lymphatic endothelium

Summary

Summary: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces.

Top Publications

  1. Fukunaga M. Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours. Histopathology. 2005;46:396-402 pubmed
    To evaluate the expression of D2-40 in normal lymphatic endothelium and vascular tumours or tumour-like lesions of the skin and soft tissue...
  2. Sawa Y, Sugimoto Y, Ueki T, Ishikawa H, Sato A, Nagato T, et al. Effects of TNF-alpha on leukocyte adhesion molecule expressions in cultured human lymphatic endothelium. J Histochem Cytochem. 2007;55:721-33 pubmed
    ..This suggests that the lymphatic endothelium has the TNF-alpha-induced signaling pathway, resulting in increased VCAM-1 and ICAM-1 expression to a ..
  3. Norgall S, Papoutsi M, Rossler J, Schweigerer L, Wilting J, Weich H. Elevated expression of VEGFR-3 in lymphatic endothelial cells from lymphangiomas. BMC Cancer. 2007;7:105 pubmed
    ..We addressed this problem by profiling LECs from normal dermis and two children suffering from lymphangioma, and also compared them with blood endothelial cells (BECs) from umbilical vein, aorta and myometrial microvessels...
  4. Karpanen T, Alitalo K. Molecular biology and pathology of lymphangiogenesis. Annu Rev Pathol. 2008;3:367-97 pubmed
    ..Recently, several markers specific for lymphatic endothelium and models for lymphatic vascular research have been characterized, enabling great technical progress in ..
  5. Jeltsch M, Tammela T, Alitalo K, Wilting J. Genesis and pathogenesis of lymphatic vessels. Cell Tissue Res. 2003;314:69-84 pubmed
    ..Here, we give an overview of the structure, function, and development of the lymphatics, with special emphasis on the recently discovered lymphangiogenic growth factors...
  6. Abtahian F, Guerriero A, Sebzda E, Lu M, Zhou R, Mocsai A, et al. Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science. 2003;299:247-51 pubmed
    ..These studies reveal a hematopoietic signaling pathway required for separation of the two major vascular networks in mammals...
  7. Wilting J, Papoutsi M, Christ B, Nicolaides K, Von Kaisenberg C, Borges J, et al. The transcription factor Prox1 is a marker for lymphatic endothelial cells in normal and diseased human tissues. FASEB J. 2002;16:1271-3 pubmed
    ..VEGFR-3 and CD34 are less reliable markers for LECs and BECs, respectively, because exceptions from their normal expression patterns are found in pathologic tissues...
  8. Irjala H, Elima K, Johansson E, Merinen M, Kontula K, Alanen K, et al. The same endothelial receptor controls lymphocyte traffic both in vascular and lymphatic vessels. Eur J Immunol. 2003;33:815-24 pubmed
    ..molecule designated common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) on human lymphatic endothelium and high endothelial venules...
  9. Schledzewski K, Falkowski M, Moldenhauer G, Metharom P, Kzhyshkowska J, Ganss R, et al. Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4/80+, CD11b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangi. J Pathol. 2006;209:67-77 pubmed
    ..prognostic parameter for several cancers that is preferentially quantified by immunohistochemistry of the lymphatic endothelium-specific hyaluronan receptor LYVE-1...

More Information

Publications62

  1. Sawa Y, Tsuruga E, Iwasawa K, Ishikawa H, Yoshida S. Leukocyte adhesion molecule and chemokine production through lipoteichoic acid recognition by toll-like receptor 2 in cultured human lymphatic endothelium. Cell Tissue Res. 2008;333:237-52 pubmed publisher
    We have recently reported that the human lymphatic endothelium has toll-like receptor 4 (TLR4)-mediated lipopolysaccharide recognition mechanisms that induce the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell ..
  2. Jurisic G, Detmar M. Lymphatic endothelium in health and disease. Cell Tissue Res. 2009;335:97-108 pubmed publisher
    ..This has also led to new insights into the role of lymphatic endothelium in a number of diseases, including primary and secondary lymphedemas...
  3. Nightingale T, Frayne M, Clasper S, Banerji S, Jackson D. A mechanism of sialylation functionally silences the hyaluronan receptor LYVE-1 in lymphatic endothelium. J Biol Chem. 2009;284:3935-45 pubmed publisher
    ..These results reveal unexpected complexity in the regulation of LYVE-1 function and raise the possibility that this receptor, like CD44, may become active after appropriate unmasking in vivo...
  4. Pepper M, Skobe M. Lymphatic endothelium: morphological, molecular and functional properties. J Cell Biol. 2003;163:209-13 pubmed
    ..This overview highlights recent advances in our understanding of the molecular mechanisms underlying the formation and function of lymphatic vessels...
  5. Salven P, Mustjoki S, Alitalo R, Alitalo K, Rafii S. VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells. Blood. 2003;101:168-72 pubmed
  6. Peyrot S, Martin B, Harland R. Lymph heart musculature is under distinct developmental control from lymphatic endothelium. Dev Biol. 2010;339:429-38 pubmed publisher
    ..and upon en1 knockdown, lymph heart muscle fails to develop, despite the normal development of the lymphatic endothelium of the lymph heart, and embryos develop edema...
  7. Irjala H, Johansson E, Grenman R, Alanen K, Salmi M, Jalkanen S. Mannose receptor is a novel ligand for L-selectin and mediates lymphocyte binding to lymphatic endothelium. J Exp Med. 2001;194:1033-42 pubmed
    ..In this work we have identified mannose receptor (MR) on human lymphatic endothelium and demonstrate its involvement in binding of lymphocytes to lymphatic vessels...
  8. Nibbs R, Kriehuber E, Ponath P, Parent D, Qin S, Campbell J, et al. The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors. Am J Pathol. 2001;158:867-77 pubmed
  9. Karkkainen M, Makinen T, Alitalo K. Lymphatic endothelium: a new frontier of metastasis research. Nat Cell Biol. 2002;4:E2-5 pubmed
    ..Recent developments have highlighted the importance of lymphatic ECs, and they could become the next focus for angiogenesis and metastasis research...
  10. Gunn M, Tangemann K, Tam C, Cyster J, Rosen S, Williams L. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. Proc Natl Acad Sci U S A. 1998;95:258-63 pubmed
    ..nodes and Peyer's patches, in the T cell areas of spleen, lymph nodes, and Peyer's patches, and in the lymphatic endothelium of multiple organs...
  11. Podgrabinska S, Braun P, Velasco P, Kloos B, Pepper M, Skobe M. Molecular characterization of lymphatic endothelial cells. Proc Natl Acad Sci U S A. 2002;99:16069-74 pubmed
    ..The molecular profile of lymphatic endothelium seems to reflect characteristic functional and structural features of the lymphatic capillaries...
  12. Ji R. Lymphatic endothelial cells, inflammatory lymphangiogenesis, and prospective players. Curr Med Chem. 2007;14:2359-68 pubmed
    ..Increased knowledge of LEC-specific modulators in inflammatory microenvironment is vital for prevention and treatment of lymphatic-associated diseases...
  13. Johnson L, Jackson D. Cell traffic and the lymphatic endothelium. Ann N Y Acad Sci. 2008;1131:119-33 pubmed publisher
    ..Here we review the current knowledge of leukocyte trans-lymphatic endothelial migration and its role in the development of an immune response...
  14. Podgrabinska S, Kamalu O, Mayer L, Shimaoka M, Snoeck H, Randolph G, et al. Inflamed lymphatic endothelium suppresses dendritic cell maturation and function via Mac-1/ICAM-1-dependent mechanism. J Immunol. 2009;183:1767-79 pubmed publisher
    ..potent APCs, exit tissues via lymphatic vessels, but the mechanisms of interaction between DCs and the lymphatic endothelium and the potential implications of these interactions for immune responses are poorly understood...
  15. Sawa Y, Tsuruga E. The expression of E-selectin and chemokines in the cultured human lymphatic endothelium with lipopolysaccharides. J Anat. 2008;212:654-63 pubmed publisher
    ..vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expressions in the lymphatic endothelium with lipopolysaccharides did not change at 0...
  16. Sleeman J, Krishnan J, Kirkin V, Baumann P. Markers for the lymphatic endothelium: in search of the holy grail?. Microsc Res Tech. 2001;55:61-9 pubmed
    ..suggests that differences which could function as markers to allow discrimination between blood and lymphatic endothelium should exist...
  17. Arigami T, Natsugoe S, Uenosono Y, Arima H, Mataki Y, Ehi K, et al. Lymphatic invasion using D2-40 monoclonal antibody and its relationship to lymph node micrometastasis in pN0 gastric cancer. Br J Cancer. 2005;93:688-93 pubmed
    ..We demonstrated a high incidence of micrometastasis and lymphatic invasion and a correlation between them even in pN0 gastric cancer. When planning less invasive treatment, the presence of such occult cancer cells should be considered...
  18. Stein J, Rot A, Luo Y, Narasimhaswamy M, Nakano H, Gunn M, et al. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial ve. J Exp Med. 2000;191:61-76 pubmed
    ..This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs...
  19. He Y, Rajantie I, Ilmonen M, Makinen T, Karkkainen M, Haiko P, et al. Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis. Cancer Res. 2004;64:3737-40 pubmed
  20. Sawa Y, Ueki T, Hata M, Iwasawa K, Tsuruga E, Kojima H, et al. LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 expression in human lymphatic endothelium. J Histochem Cytochem. 2008;56:97-109 pubmed
    ..The signal transduction of NF-kappaB and AP-1-dependent pathway may be more critical for the expression of IL-6 and VCAM-1 than that of IL-8 and ICAM-1 in LEC...
  21. Rouzaut A, Garasa S, Teijeira A, Gonzalez I, Martinez Forero I, Suarez N, et al. Dendritic cells adhere to and transmigrate across lymphatic endothelium in response to IFN-?. Eur J Immunol. 2010;40:3054-63 pubmed publisher
    ..Cultured lymphatic endothelium monolayers pretreated with TNF-? were used to model this phenomenon under inflammatory conditions...
  22. Jiang S, Bailey A, Goldman D, Swain J, Wong M, Streeter P, et al. Hematopoietic stem cells contribute to lymphatic endothelium. PLoS ONE. 2008;3:e3812 pubmed publisher
    ..the embryo, little is known about the role of circulating progenitors in the maintenance or development of lymphatic endothelium. Here, we investigated whether hematopoietic stem cells (HSCs) have the potential to give rise to ..
  23. Ezaki T, Kuwahara K, Morikawa S, Shimizu K, Sakaguchi N, Matsushima K, et al. Production of two novel monoclonal antibodies that distinguish mouse lymphatic and blood vascular endothelial cells. Anat Embryol (Berl). 2006;211:379-93 pubmed
    ..immunoreactivity was strongly expressed on pinocytic or transport vesicle membrane in the cytoplasm of lymphatic endothelium. Besides endothelial cells, both antibodies also recognized some types of lymphoid cells...
  24. Kahn H, Marks A. A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Invest. 2002;82:1255-7 pubmed
  25. Young A, Seabrook T, Marston W, Dudler L, Hay J. A role for lymphatic endothelium in the sequestration of recirculating gamma delta T cells in TNF-alpha-stimulated lymph nodes. Eur J Immunol. 2000;30:327-34 pubmed
    ..with VCAM-1-expressing cells in TNF-stimulated lymph nodes, at least some of which appeared to be lymphatic endothelium. These data indicate that TNF-alpha is capable of altering the number and specificity of lymphocytes ..
  26. Sakamoto M, Shimada M, Fujimaki Y, Ewert A. Degenerative changes in lymphatic endothelium of jirds infected with Brugia pahangi. J Parasitol. 1988;74:731-4 pubmed
    ..The mean +/- SD diameter of vesicles in cells from lymphatic vessels at 10 mo after infection was significantly smaller (78.6 +/- 5.6 nm) compared to vesicles in uninfected vessels (87.5 +/- 9.7 nm)...
  27. Evangelou E, Kyzas P, Trikalinos T. Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach. Mod Pathol. 2005;18:1490-7 pubmed
    Tumor lymphatic density is evaluated by means of specific lymphatic endothelium markers, and is a potential predictor of clinically meaningful outcomes...
  28. Jurisic G, Iolyeva M, Proulx S, Halin C, Detmar M. Thymus cell antigen 1 (Thy1, CD90) is expressed by lymphatic vessels and mediates cell adhesion to lymphatic endothelium. Exp Cell Res. 2010;316:2982-92 pubmed publisher
    ..Together, these results identify Thy1 as a novel lymphatic vessel expressed gene and suggest its potential role in the cell adhesion processes required for tumor progression and inflammation...
  29. Nisato R, Harrison J, Buser R, Orci L, Rinsch C, Montesano R, et al. Generation and characterization of telomerase-transfected human lymphatic endothelial cells with an extended life span. Am J Pathol. 2004;165:11-24 pubmed
    ..The production and characterization of hTERT-HDLEC will facilitate the study of the properties of lymphatic endothelium in vitro.
  30. Aurrand Lions M, Duncan L, Ballestrem C, Imhof B. JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells. J Biol Chem. 2001;276:2733-41 pubmed
    ..Taken together, our results suggest that JAM-2 is a novel vascular molecule, which participates in interendothelial junctional complexes...
  31. Witte M, Bernas M, Martin C, Witte C. Lymphangiogenesis and lymphangiodysplasia: from molecular to clinical lymphology. Microsc Res Tech. 2001;55:122-45 pubmed
  32. Petrova T, Makinen T, Makela T, Saarela J, Virtanen I, Ferrell R, et al. Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J. 2002;21:4593-9 pubmed
    ..Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells...
  33. Kahn H, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi's sarcoma and a subset of angiosarcomas. Mod Pathol. 2002;15:434-40 pubmed
    ..antibody to an Mr 40,000 O-linked sialoglycoprotein that reacts with a fixation-resistant epitope on lymphatic endothelium. We sought to establish the selectivity of D2-40 for lymphatic endothelium in normal tissues and compare ..
  34. Shin J, Huggenberger R, Detmar M. Transcriptional profiling of VEGF-A and VEGF-C target genes in lymphatic endothelium reveals endothelial-specific molecule-1 as a novel mediator of lymphangiogenesis. Blood. 2008;112:2318-26 pubmed publisher
    ..We aimed to comprehensively identify downstream molecular targets induced by VEGF-A or VEGF-C in lymphatic endothelium by analyzing the time-series transcriptional profile of treated human dermal lymphatic endothelial cells (..
  35. Miteva D, Rutkowski J, Dixon J, Kilarski W, Shields J, Swartz M. Transmural flow modulates cell and fluid transport functions of lymphatic endothelium. Circ Res. 2010;106:920-31 pubmed publisher
  36. Kaipainen A, Korhonen J, Mustonen T, van Hinsbergh V, Fang G, Dumont D, et al. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci U S A. 1995;92:3566-70 pubmed
    ..Our results suggest that FLT4 is a marker for lymphatic vessels and some high endothelial venules in human adult tissues. They also support the theory on the venous origin of lymphatic vessels...
  37. Wigle J, Oliver G. Prox1 function is required for the development of the murine lymphatic system. Cell. 1999;98:769-78 pubmed
    ..These findings suggest that Prox1 is a specific and required regulator of the development of the lymphatic system and that the vascular and lymphatic systems develop independently...
  38. Shin J, Min M, Larrieu Lahargue F, Canron X, Kunstfeld R, Nguyen L, et al. Prox1 promotes lineage-specific expression of fibroblast growth factor (FGF) receptor-3 in lymphatic endothelium: a role for FGF signaling in lymphangiogenesis. Mol Biol Cell. 2006;17:576-84 pubmed
    ..Together, these results indicate that FGFR-3 is an initial target of Prox1 during the lymphatic cell fate specification and that FGF signaling may play an important role in lymphatic vessel development. ..
  39. Farnsworth R, Achen M, Stacker S. Lymphatic endothelium: an important interactive surface for malignant cells. Pulm Pharmacol Ther. 2006;19:51-60 pubmed
    ..This review provides a synopsis of the recent data pertaining to the purification and culture of lymphatic endothelial cells, and the interaction of tumour cells with lymphatic endothelium.
  40. He Y, Rajantie I, Pajusola K, Jeltsch M, Holopainen T, Yla Herttuala S, et al. Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels. Cancer Res. 2005;65:4739-46 pubmed
    ..This indicates that complete blockade of lymphatic metastasis may require the targeting of both tumor lymphangiogenesis and tumor cell invasion...
  41. Palframan R, Jung S, Cheng G, Weninger W, Luo Y, Dorf M, et al. Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J Exp Med. 2001;194:1361-73 pubmed
  42. Irjala H, Alanen K, Grenman R, Heikkila P, Joensuu H, Jalkanen S. Mannose receptor (MR) and common lymphatic endothelial and vascular endothelial receptor (CLEVER)-1 direct the binding of cancer cells to the lymph vessel endothelium. Cancer Res. 2003;63:4671-6 pubmed
    ..lymphatic endothelial and vascular endothelial receptor (CLEVER)-1 in adhesion of malignant cells to the lymphatic endothelium, and analyzed their expression in two clinical series consisting of squamous cell cancers of the head and ..
  43. Wilting J, Papoutsi M, Schneider M, Christ B. The lymphatic endothelium of the avian wing is of somitic origin. Dev Dyn. 2000;217:271-8 pubmed
    ..This shows that not only the blood vascular cells but also the lymphatic endothelial cells of the avian wing are born in the paraxial/somitic mesoderm...
  44. Sacchi G, Weber E, Agliano M, Cavina N, Comparini L. Lymphatic vessels of the human heart: precollectors and collecting vessels. A morpho-structural study. J Submicrosc Cytol Pathol. 1999;31:515-25 pubmed
  45. Salomonsson S, Jonsson M, Skarstein K, Brokstad K, Hjelmstrom P, Wahren Herlenius M, et al. Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjögren's syndrome. Arthritis Rheum. 2003;48:3187-201 pubmed
    ..To investigate functional properties of the germinal center (GC)-like structures observed in salivary glands of patients with Sjögren's syndrome (SS) and to determine the frequency with which such structures develop...
  46. Ji R, Qu P, Kato S. Application of a new 5'-nase monoclonal antibody specific for lymphatic endothelial cells. Lab Invest. 2003;83:1681-3 pubmed
  47. Mizuno R, Yokoyama Y, Ono N, Ikomi F, Ohhashi T. Establishment of rat lymphatic endothelial cell line. Microcirculation. 2003;10:127-31 pubmed
    ..The objective of the present study was to establish a rat lymphatic endothelial cell line and then to investigate the morphological and immunohistochemical properties of the cells...
  48. Kalof A, Cooper K. D2-40 immunohistochemistry--so far!. Adv Anat Pathol. 2009;16:62-4 pubmed publisher
    ..This brief review provides an update on the ever-expanding proposed applications of D2-40 immunohistochemistry in surgical pathology...
  49. Adachi Y, Nakamura H, Kitamura Y, Taniguchi Y, Araki K, Shomori K, et al. Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases. Pathol Int. 2007;57:171-7 pubmed
    ..LVI based on the immunohistochemical expression of podoplanin or D2-40, which are new specific markers for lymphatic endothelium. Using 76 cases of pulmonary adenocarcinoma, the relationship between LVD and LVI, lymph node metastases, ..
  50. Gannon B, Carati C. Endothelial distribution of the membrane water channel molecule aquaporin-1: implications for tissue and lymph fluid physiology?. Lymphat Res Biol. 2003;1:55-66 pubmed
    ..We investigated endothelial AQ-1 expression in rat intestine and mesentery, and also in lymph nodes...
  51. Ando T, Jordan P, Joh T, Wang Y, Jennings M, Houghton J, et al. Isolation and characterization of a novel mouse lymphatic endothelial cell line: SV-LEC. Lymphat Res Biol. 2005;3:105-15 pubmed
    ..g., Prox-1, LYVE-1, Flt-4). SV-LEC also expresses MAdCAM-1 in response to TNF-alpha, an effect seen in VEC, but not AEC...
  52. Shao X, Chi X. Influence of angiostatin and thalidomide on lymphangiogenesis. Lymphology. 2005;38:146-55 pubmed
    ..We conclude that both angiostatin and thalidomide are able to inhibit LE cell growth in a dose-dependent manner and that the inhibition may be through induction of apoptosis...
  53. Dickinson A, Gausas R. Orbital lymphatics: do they exist?. Eye (Lond). 2006;20:1145-8 pubmed
    ..Through advances in molecular biology and the development of endothelial cell markers the long held view that the human orbit is devoid of lymphatics has now been challenged...