BACKGROUND: Although lymph node transplantation has been shown to improve lymphatic function, the mechanisms regulating lymphatic vessel reconnection and functional status of lymph nodes remains poorly understood. METHODS: The authors developed and used LacZ lymphatic reporter mice to examine the lineage of lymphatic vessels infiltrating transferred lymph nodes. In addition, the authors analyzed lymphatic function, expression of vascular endothelial growth factor (VEGF)-C, maintenance of T- and B-cell zone, and anatomical localization of lymphatics and high endothelial venules. RESULTS: Reporter mice were specific and highly sensitive in identifying lymphatic vessels. Lymph node transfer was associated with rapid return of lymphatic function and clearance of technetium-99 secondary to a massive infiltration of recipient mouse lymphatics and putative connections to donor lymphatics. T- and B-cell populations in the lymph node were maintained. These changes correlated with marked increases in the expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Newly formed lymphatic channels in transferred lymph nodes were in close anatomical proximity to high endothelial venules. CONCLUSIONS: Transferred lymph nodes have rapid infiltration of functional host lymphatic vessels and maintain T- and B-cell populations. This process correlates with increased endogenous expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Anatomical proximity of newly formed lymphatics and high endothelial venules supports the hypothesis that lymph node transfer can improve lymphedema by exchanges with the systemic circulation.
BACKGROUND: Although lymph node transplantation has been shown to improve lymphatic function, the mechanisms regulating lymphatic vessel reconnection and functional status of lymph nodes remains poorly understood. METHODS: The authors developed and used LacZ lymphatic reporter mice to examine the lineage of lymphatic vessels infiltrating transferred lymph nodes. In addition, the authors analyzed lymphatic function, expression of vascular endothelial growth factor (VEGF)-C, maintenance of T- and B-cell zone, and anatomical localization of lymphatics and high endothelial venules. RESULTS: Reporter mice were specific and highly sensitive in identifying lymphatic vessels. Lymph node transfer was associated with rapid return of lymphatic function and clearance of technetium-99 secondary to a massive infiltration of recipient mouse lymphatics and putative connections to donor lymphatics. T- and B-cell populations in the lymph node were maintained. These changes correlated with marked increases in the expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Newly formed lymphatic channels in transferred lymph nodes were in close anatomical proximity to high endothelial venules. CONCLUSIONS: Transferred lymph nodes have rapid infiltration of functional host lymphatic vessels and maintain T- and B-cell populations. This process correlates with increased endogenous expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Anatomical proximity of newly formed lymphatics and high endothelial venules supports the hypothesis that lymph node transfer can improve lymphedema by exchanges with the systemic circulation.
Authors: Daniel A Cuzzone; Nicholas J Albano; Seth Z Aschen; Swapna Ghanta; Babak J Mehrara Journal: Lymphat Res Biol Date: 2014-08-21 Impact factor: 2.589
Authors: Jason C Gardenier; Geoffrey E Hespe; Raghu P Kataru; Ira L Savetsky; Jeremy S Torrisi; Gabriela D García Nores; Joseph J Dayan; David Chang; Jamie Zampell; Inés Martínez-Corral; Sagrario Ortega; Babak J Mehrara Journal: JCI Insight Date: 2016-09-22
Authors: Sinem Karaman; Maija Hollmén; Marius R Robciuc; Annamari Alitalo; Harri Nurmi; Bettina Morf; Dorina Buschle; H Furkan Alkan; Alexandra M Ochsenbein; Kari Alitalo; Christian Wolfrum; Michael Detmar Journal: Mol Metab Date: 2014-12-04 Impact factor: 7.422
Authors: Florian S Frueh; Christina Körbel; Laura Gassert; Andreas Müller; Epameinondas Gousopoulos; Nicole Lindenblatt; Pietro Giovanoli; Matthias W Laschke; Michael D Menger Journal: Sci Rep Date: 2016-10-04 Impact factor: 4.379
Authors: G D García Nores; D A Cuzzone; N J Albano; G E Hespe; R P Kataru; J S Torrisi; J C Gardenier; I L Savetsky; S Z Aschen; M D Nitti; B J Mehrara Journal: Int J Obes (Lond) Date: 2016-05-20 Impact factor: 5.095