Mechanosensing in Developing Lymphatic Vessels
The lymphatic vasculature is responsible for fluid homeostasis, transport of immune cells, inflammatory molecules, and dietary lipids. It is composed of a network of lymphatic capillaries that drain into collecting lymphatic vessels and ultimately bring f
- PDF / 280,671 Bytes
- 18 Pages / 439.37 x 666.142 pts Page_size
- 78 Downloads / 189 Views
Mechanosensing in Developing Lymphatic Vessels Lara Planas-Paz and Eckhard Lammert
Abstract The lymphatic vasculature is responsible for fluid homeostasis, transport of immune cells, inflammatory molecules, and dietary lipids. It is composed of a network of lymphatic capillaries that drain into collecting lymphatic vessels and ultimately bring fluid back to the blood circulation. Lymphatic endothelial cells (LECs) that line lymphatic capillaries present loose overlapping intercellular junctions and anchoring filaments that support fluid drainage. When interstitial fluid accumulates within tissues, the extracellular matrix (ECM) swells and pulls the anchoring filaments. This results in opening of the LEC junctions and permits interstitial fluid uptake. The absorbed fluid is then transported within collecting lymphatic vessels, which exhibit intraluminal valves that prevent lymph backflow and smooth muscle cells that sequentially contract to propel lymph. Mechanotransduction involves translation of mechanical stimuli into biological responses. LECs have been shown to sense and respond to changes in ECM stiffness, fluid pressure-induced cell stretch, and fluid flow-induced shear stress. How these signals influence LEC function and lymphatic vessel growth can be investigated by using different mechanotransduction assays in vitro and to some extent in vivo. In this chapter, we will focus on the mechanical forces that regulate lymphatic vessel expansion during embryonic development and possibly secondary lymphedema. In mouse embryos, it has been recently shown that the amount of interstitial fluid determines the extent of lymphatic vessel expansion via a mechanosensory L. Planas-Paz Institute of Metabolic Physiology, Heinrich-Heine University, Universita¨tsstrasse 1, 40225 Du¨sseldorf, Germany E. Lammert (*) Institute of Metabolic Physiology, Heinrich-Heine University, Universita¨tsstrasse 1, 40225 Du¨sseldorf, Germany Paul-Langerhans-Group for Beta Cell Biology, German Diabetes Center (DDZ), Auf’m Hennekamp 65, 40225 Du¨sseldorf, Germany 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_3, © Springer-Verlag Wien 2014
23
24
L. Planas-Paz and E. Lammert
complex formed by β1 integrin and vascular endothelial growth factor receptor-3 (VEGFR3). This model might as well apply to secondary lymphedema.
3.1 3.1.1
Entry of Interstitial Fluid into Lymphatic Capillaries Interstitial Fluid Drainage
Lymphatic capillaries are blind-ended and are surrounded by a discontinuous basement membrane (Schulte-Merker et al. 2011). They are composed of LECs that exhibit oak leaf shape and discontinuous button-like junctions that overlap at cell edges (Baluk et al. 2007). LECs are tethered to the surrounding ECM in part via anchoring filaments composed of emilin-1 and fibrillin (Leak and Burke 1968a, b; Maby-El Hajjami 2008). The current model of fluid uptake by lymphatic ca
Data Loading...
