Molecular and cellular basis of the regulation of lymphatic contractility and lymphatic absorption

Lymphatic absorption is a highly regulated process driven by both an extrinsic mechanism (external force) and an intrinsic mechanism (lymphatic vessel contractility). The lymphatic muscle is a specialized smooth muscle with unique mechanical properties. To understand the molecular mechanism and rela...

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Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2014-08, Vol.53, p.134-140
Main Authors: Wang, Yu, Zhao, Wei, Zhang, Lin, Zhao, Yong-Na, Li, Fei, Zhang, Zhen, Dai, Yun-Dong, Li, Wei-Feng, Qiao, Yan-Ning, Chen, Cai-Ping, Gao, Ji-Min, Zhu, Min-Sheng
Format: Article
Language:English
Subjects:
Animals
Contractility, Absorption
Humans
Lymphatic vessel
Lymphatic Vessels - metabolism
Lymphatic Vessels - physiology
Mice
Mice, Transgenic
Muscle Contraction - genetics
Muscle, Smooth - metabolism
Mutation
Myosin light chain kinase
Myosin Light Chains - genetics
Myosin-Light-Chain Kinase - genetics
Myosin-Light-Chain Kinase - metabolism
Smooth muscle
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Summary:Lymphatic absorption is a highly regulated process driven by both an extrinsic mechanism (external force) and an intrinsic mechanism (lymphatic vessel contractility). The lymphatic muscle is a specialized smooth muscle with unique mechanical properties. To understand the molecular mechanism and relative contribution of smooth muscle contraction in lymphatic absorption, we analyzed mice with a smooth muscle-specific deletion of Mylk, a critical gene for smooth muscle contraction. Interestingly, the knockout mice were significantly resistant to anesthesia reagents. Upon injection in the feet with FITC-dextran, the mutant mice displayed a 2-fold delay of the absorption peak in the peripheral circulation. Examining the ear lymphatic vessels of the mutant mice revealed a reduction in the amount of fluid in the lumens of the lymphangions, suggesting an impairment of lymph formation. The Mylk-deficient lymphatic muscle exhibited a significant reduction of peristalsis and of myosin light chain phosphorylation in response to depolarization. We thus concluded that MLCK and myosin light chain phosphorylation are required for lymphatic vessel contraction. Lymphatic contractility is not an exclusive requirement for lymphatic absorption, and external force appears to be necessary for absorption.
ISSN:1357-2725
1878-5875
DOI:10.1016/j.biocel.2014.05.002