Retrograde Lymph Flow Leads to Chylothorax in Transgenic Mice with Lymphatic Malformations

Show full item record



Permalink

http://hdl.handle.net/10138/297947

Citation

Nitschke , M , Bell , A , Karaman , S , Amouzgar , M , Rutkowski , J M , Scherer , P E , Alitalo , K & McDonald , D M 2017 , ' Retrograde Lymph Flow Leads to Chylothorax in Transgenic Mice with Lymphatic Malformations ' , The American Journal of Pathology , vol. 187 , no. 9 , pp. 1984-1997 . https://doi.org/10.1016/j.ajpath.2017.05.009

Title: Retrograde Lymph Flow Leads to Chylothorax in Transgenic Mice with Lymphatic Malformations
Author: Nitschke, Maximilian; Bell, Alexander; Karaman, Sinem; Amouzgar, Meelad; Rutkowski, Joseph M.; Scherer, Philipp E.; Alitalo, Kari; McDonald, Donald M.
Contributor: University of Helsinki, Translational Cancer Biology (TCB) Research Programme
University of Helsinki, University of Helsinki
Date: 2017-09
Language: eng
Number of pages: 14
Belongs to series: The American Journal of Pathology
ISSN: 0002-9440
URI: http://hdl.handle.net/10138/297947
Abstract: Chylous pleural effusion (chylothorax) frequently accompanies lymphatic vessel malformations and other conditions with lymphatic defects. Although retrograde flow of chyle from the thoracic duct is considered a potential mechanism underlying chylothorax in patients and mouse models, the path chyle takes to reach the thoracic cavity is unclear. Herein, we use a novel transgenic mouse model, where doxycycline-induced overexpression of vascular endothelial growth factor (VEGF)-C was driven by the adipocyte-specific promoter adiponectin (ADN), to determine how chylothorax forms. Surprisingly, 100% of adult ADN-VEGF-C mice developed chylothorax within 7 days. Rapid, consistent appearance of chylothorax enabled us to examine the step-by-step development in otherwise normal adult mice. Dynamic imaging with a fluorescent tracer revealed that lymph in the thoracic duct of these mice could enter the thoracic cavity by retrograde flow into enlarged paravertebral Lymphatics and subpleural lymphatic plexuses that had incompetent Lymphatic valves. Pleural mesothelium overlying the lymphatic plexuses underwent exfoliation that increased during doxycycline exposure. Together, the findings indicate that chylothorax in ADN-VEGF-C mice results from retrograde flow of chyle from the thoracic duct into lymphatic tributaries with defective valves. Chyle extravasates from these plexuses and enters the thoracic cavity through exfoliated regions of the pleural mesothelium.
Subject: GROWTH FACTOR-C
VALVE DEVELOPMENT
PLEURAL LIQUID
ENDOTHELIAL-CELLS
HYDROPS-FETALIS
CHYLOUS REFLUX
IN-VIVO
VESSELS
LYMPHANGIOGENESIS
VASCULATURE
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S0002944017300433_main.pdf 5.620Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record