Plasticity of Airway Lymphatics in Development and Disease
The dynamic nature of lymphatic vessels is reflected by structural and functional modifications that coincide with changes in their environment. Lymphatics in the respiratory tract undergo rapid changes around birth, during adaptation to air breathing, wh
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Plasticity of Airway Lymphatics in Development and Disease Li-Chin Yao and Donald M. McDonald
Abstract The dynamic nature of lymphatic vessels is reflected by structural and functional modifications that coincide with changes in their environment. Lymphatics in the respiratory tract undergo rapid changes around birth, during adaptation to air breathing, when lymphatic endothelial cells develop button-like intercellular junctions specialized for efficient fluid uptake and transport. In inflammatory conditions, lymphatic vessels proliferate and undergo remodeling to accommodate greater plasma leakage and immune cell trafficking. However, the newly formed lymphatics are abnormal, and resolution of inflammation is not accompanied by complete reversal of the lymphatic vessel changes back to the baseline. As the understanding of lymphatic plasticity advances, approaches for eliminating the abnormal vessels and improving the functionality of those that remain move closer to reality. This chapter provides an overview of what is known about lymphatic vessel growth, remodeling, and other forms of plasticity that occur during development or inflammation, with an emphasis on the respiratory tract. Also addressed is the limited reversibility of changes in lymphatics during the resolution of inflammation.
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Introduction
Plasma leakage, edema, and remodeling of the airway wall are hallmarks of inflammatory airway diseases (Dunnill 1960; Ebina 2008; Wilson and Hii 2006). Lymphangiogenesis and lymphatic remodeling are among the features of sustained respiratory inflammation (El-Chemaly et al. 2008). Lymphatics proliferate in pneumonia (Mandal et al. 2008; Parra et al. 2012), regress in asthma (Ebina et al. 2010), and undergo remodeling and growth in idiopathic pulmonary fibrosis (Yamashita L.-C. Yao • D.M. McDonald (*) Department of Anatomy, Comprehensive Cancer Center, Cardiovascular Research Institute, University of California-San Francisco, San Francisco, CA 94143, USA e-mail: [email protected] F. Kiefer and S. Schulte-Merker (eds.), Developmental Aspects of the Lymphatic Vascular System, Advances in Anatomy, Embryology and Cell Biology 214, DOI 10.1007/978-3-7091-1646-3_4, © Springer-Verlag Wien 2014
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et al. 2009; El-Chemaly et al. 2009). Understanding the contribution of lymphatic changes to disease pathophysiology and the clinical implications is still at an early stage. Elucidation of the causes, consequences, and reversibility of changes in airway lymphatics will offer new therapeutic targets and treatment strategies. In a mouse model of sustained inflammation associated with infection by the respiratory pathogen Mycoplasma pulmonis, lymphatics in the airways and lung undergo rapid proliferation and remodeling (Baluk et al. 2005; McDonald 2008). Lymphatic growth and remodeling typically occur together but represent different vascular responses, and the driving factors and consequences are likely to be different. As diseases worsen, the lymphatic microvasculature undergoes p
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