Liver lymphatic drainage patterns follow segmental anatomy in a murine model

Abstract The liver’s cellular functions are sustained by a hierarchical, segmentally-organized vascular system. Additionally, liver lymphatic vessels are thought to drain to perihepatic lymph nodes. Surprisingly, while recent findings highlight the importance of organ-specific lymphatics, the functi...

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Main Authors: Nicola C. Frenkel, Susanna Poghosyan, André Verheem, Timothy P. Padera, Inne H. M. Borel Rinkes, Onno Kranenburg, Jeroen Hagendoorn
Format: Article
Language:English
Published: Nature Publishing Group 2020-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-78727-y
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spelling doaj-83a9268bbc9c4e1cb850f89e226f267c2020-12-13T12:34:29ZengNature Publishing GroupScientific Reports2045-23222020-12-011011910.1038/s41598-020-78727-yLiver lymphatic drainage patterns follow segmental anatomy in a murine modelNicola C. Frenkel0Susanna Poghosyan1André Verheem2Timothy P. Padera3Inne H. M. Borel Rinkes4Onno Kranenburg5Jeroen Hagendoorn6Laboratory for Translational Oncology, Cancer Center, University Medical Center Utrecht and Utrecht UniversityLaboratory for Translational Oncology, Cancer Center, University Medical Center Utrecht and Utrecht UniversityLaboratory for Translational Oncology, Cancer Center, University Medical Center Utrecht and Utrecht UniversityE.L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical SchoolLaboratory for Translational Oncology, Cancer Center, University Medical Center Utrecht and Utrecht UniversityLaboratory for Translational Oncology, Cancer Center, University Medical Center Utrecht and Utrecht UniversityLaboratory for Translational Oncology, Cancer Center, University Medical Center Utrecht and Utrecht UniversityAbstract The liver’s cellular functions are sustained by a hierarchical, segmentally-organized vascular system. Additionally, liver lymphatic vessels are thought to drain to perihepatic lymph nodes. Surprisingly, while recent findings highlight the importance of organ-specific lymphatics, the functional anatomy of liver lymphatics has not been mapped out. In literature, no segmental or preferential lymphatic drainage patterns are known to exist. We employ a novel murine model of liver lymphangiography and in vivo microscopy to delineate the lymphatic drainage patterns of individual liver lobes. Our data from blue dye liver lymphangiography show preferential lymphatic drainage patterns: Right lobe mainly to hepatoduodenal ligament lymph node 1 (LN1); left lobe to hepatoduodenal ligament LN1 + LN2 concurrently; median lobe showed a more variable LN1/LN2 drainage pattern with increased (sometimes exclusive) mediastinal thoracic lymph node involvement, indicating that part of the liver can drain directly to the mediastinum. Upon ferritin lymphangiography, we observed no functional communication between the lobar lymphatics. Altogether, these results show the existence of preferential lymphatic drainage patterns in the murine liver. Moreover, this drainage can occur directly to mediastinal lymph nodes and there is no interlobar lymphatic flow. Collectively, these data provide the first direct evidence that liver lymphatic drainage patterns follow segmental anatomy.https://doi.org/10.1038/s41598-020-78727-y
collection DOAJ
language English
format Article
sources DOAJ
author Nicola C. Frenkel
Susanna Poghosyan
André Verheem
Timothy P. Padera
Inne H. M. Borel Rinkes
Onno Kranenburg
Jeroen Hagendoorn
spellingShingle Nicola C. Frenkel
Susanna Poghosyan
André Verheem
Timothy P. Padera
Inne H. M. Borel Rinkes
Onno Kranenburg
Jeroen Hagendoorn
Liver lymphatic drainage patterns follow segmental anatomy in a murine model
Scientific Reports
author_facet Nicola C. Frenkel
Susanna Poghosyan
André Verheem
Timothy P. Padera
Inne H. M. Borel Rinkes
Onno Kranenburg
Jeroen Hagendoorn
author_sort Nicola C. Frenkel
title Liver lymphatic drainage patterns follow segmental anatomy in a murine model
title_short Liver lymphatic drainage patterns follow segmental anatomy in a murine model
title_full Liver lymphatic drainage patterns follow segmental anatomy in a murine model
title_fullStr Liver lymphatic drainage patterns follow segmental anatomy in a murine model
title_full_unstemmed Liver lymphatic drainage patterns follow segmental anatomy in a murine model
title_sort liver lymphatic drainage patterns follow segmental anatomy in a murine model
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2020-12-01
description Abstract The liver’s cellular functions are sustained by a hierarchical, segmentally-organized vascular system. Additionally, liver lymphatic vessels are thought to drain to perihepatic lymph nodes. Surprisingly, while recent findings highlight the importance of organ-specific lymphatics, the functional anatomy of liver lymphatics has not been mapped out. In literature, no segmental or preferential lymphatic drainage patterns are known to exist. We employ a novel murine model of liver lymphangiography and in vivo microscopy to delineate the lymphatic drainage patterns of individual liver lobes. Our data from blue dye liver lymphangiography show preferential lymphatic drainage patterns: Right lobe mainly to hepatoduodenal ligament lymph node 1 (LN1); left lobe to hepatoduodenal ligament LN1 + LN2 concurrently; median lobe showed a more variable LN1/LN2 drainage pattern with increased (sometimes exclusive) mediastinal thoracic lymph node involvement, indicating that part of the liver can drain directly to the mediastinum. Upon ferritin lymphangiography, we observed no functional communication between the lobar lymphatics. Altogether, these results show the existence of preferential lymphatic drainage patterns in the murine liver. Moreover, this drainage can occur directly to mediastinal lymph nodes and there is no interlobar lymphatic flow. Collectively, these data provide the first direct evidence that liver lymphatic drainage patterns follow segmental anatomy.
url https://doi.org/10.1038/s41598-020-78727-y
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