Microcirculatory Exchange Function

Lymphatic Endothelial Cells Adapt Their Barrier Function in Response to Changes in Shear Stress

“…Thus, as with vascular endothelium, cAMP=PKA signaling is important for normal, baseline barrier function of lymphatic endothelial cells. 12,17,35 Mechanosensing of changes in flow rate has been documented in isolated collecting lymphatic vessels and is important for modulating the intrinsic pumping activity of lymphatic smooth muscle. 3,4,6 It is less clear what other effects that t has on lymphatic vessels, although we speculate that the changes in barrier function that we observe with cultured cells may be part of an adaptive mechanism that prevents excess leakage of fluids and solutes across the collecting lymphatic endothelium.…”

“…12,17,[22][23][24][25][26] We tested the role of this pathway by inhibiting PKA activity with the specific inhibitor H-89 (Fig. 7).…”

“…8,9 we tested the hypothesis that a step elevation of t rapidly enhances barrier function. In addition, we evaluated whether protein kinase A (PKA) or the small GTPase Rac1, both of which have been implicated as promoters of enhanced endothelial barrier function, 12 may be involved in shear stress-induced changes in lymphatic endothelial barrier function.…”

Study of the Actin Cytoskeleton in Live Endothelial Cells Expressing GFP-Actin

“…A cortical actin belt is thought to be important for the maintenance of stable junctions 1,2,4,5 . In contrast, actin stress fibers are thought to generate centripetal tension within endothelial cells that weakens junctions [2][3][4][5] . Much of this theory has been based on studies in which endothelial cells are treated with inflammatory mediators known to increase endothelial permeability, and then fixing the cells and labeling F-actin for microscopic observation.…”

“…The adhesive junctions between endothelial cells regulate permeability of the endothelium, and many studies have indicated the important contribution of the actin cytoskeleton to determining junctional integrity [1][2][3][4][5] . A cortical actin belt is thought to be important for the maintenance of stable junctions 1,2,4,5 . In contrast, actin stress fibers are thought to generate centripetal tension within endothelial cells that weakens junctions [2][3][4][5] .…”