Pre-collecting lymphatic vessels form detours following obstruction of lymphatic flow and function as collecting lymphatic vessels

Autoři: Kimi Asano aff001;  Yukari Nakajima aff003;  Kanae Mukai aff003;  Tamae Urai aff004;  Mayumi Okuwa aff003;  Junko Sugama aff005;  Chizuko Konya aff006;  Toshio Nakatani aff003
Působiště autorů: Department of Clinical Nursing, Graduate Course of Nursing Science, Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan aff001;  School of Nursing, Kanazawa Medical University, Uchinada, Japan aff002;  Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan aff003;  Faculty of Nursing, Toyama Prefectural University, Toyama, Japan aff004;  Advanced Health Care Science Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Japan aff005;  Faculty of Nursing, Ishikawa Prefectural Nursing University, Kahoku, Japan aff006
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227814



Previously, we showed that lymphatic vessels (LVs) formed detours after lymphatic obstruction, contributing to preventing lymphedema. In this study, we developed detours using lymphatic ligation in mice and we identified the detours histologically.

Methods and results

Under anesthesia, both hindlimbs in mice were subcutaneously injected with Evans blue dye to detect LVs. We tied the right collecting LV on the abdomen that passes through the inguinal lymph node (LN) at two points. The right and left sides comprised the operation and sham operation sides, respectively. Lymphography was performed to investigate the lymph flow after lymphatic ligation until day 30, using a near-infrared fluorescence imaging system. Anti-podoplanin antibody and 5-ethynyl-2’-deoxyuridine (EdU) were used to detect LVs and lymphangiogenesis. Within 30 days, detours had developed in 62.5% of the mice. Detours observed between two ligation sites were enlarged and irregular in shape. Podoplanin+ LVs, which were located in the subcutaneous tissue of the upper panniculus carnosus muscle, connected to collecting LVs at the upper portion from the cranial ligation site and at the lower portion from the caudal ligation site. EdU+ cells were not observed in these detours. The sham operation side showed normal lymph flow and did not show enlarged pre-collecting LVs until day 30.


Detours after lymphatic ligation were formed not by lymphangiogenesis but through an enlargement of pre-collecting LVs that functioned as collecting LVs after lymphatic ligation. Further studies are required to explore the developmental mechanism of the lymphatic detour for treatment and effective care of lymphedema in humans.

Klíčová slova:

Abdomen – Histology – Immunostaining – Lymph – Lymphedema – Muscle tissue – Surgical and invasive medical procedures – Subcutaneous tissue


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