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

Retrograde Lymph Flow Leads to Chylothorax in Transgenic Mice with Lymphatic Malformations.
Am J Pathol. 2017 Jul 03;:
Authors: Nitschké M, Bell A, Karaman S, Amouzgar M, Rutkowski JM, Scherer PE, Alitalo K, McDonald DM
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-V...

Source: The American Journal of Pathology - July 3, 2017 Category: Pathology Authors: Nitschké M, Bell A, Karaman S, Amouzgar M, Rutkowski JM, Scherer PE, Alitalo K, McDonald DM Tags: Am J Pathol Source Type: research