Shedding of the Endothelial Glycocalyx in Arterioles, Capillaries and Venules

Abstract

Shedding of components of the venular endothelial glycocalyx in response to shear stresses or G-protein coupled receptor stimulation with fMLP may expose EC receptors for WBC-EC adhesion, disrupt the barrier to transvascular exchange of macromolecules, or alter the effective caliber and flow resistance of microvessels. The present study aimed to examine glycan shedding throughout the hierarchy of vessels from arterioles to venules in response to fMLP stimulation. The presence and loss of glycans was probed using the lectin BS-1, labeled with the fluorescent dye Alexa-488. Binding of BS-1 was quantitated using in vivo confocal microscopy of the exteriorized mesentery (rat) prior to and following superfusion with 10−7 M fMLP. Peak fluorescence intensity of the fluorophor was obtained along the microvessel wall and corrected for background fluorescence and spatial variations in excitation. Peak value of intensity in the capillary wall prior to fMLP was typically 75% greater than those in arterioles and venules. Superfusion with fMLP caused a significant 25% decrease within 30 min exposure for arterioles, capillaries and venules. Thus, shedding of glycans appears to be present at all levels of the microvascular tree, and may affect multiple physiological processes that involve flow dependent signal transduction and/or blood cell to EC adhesion. Supported by NIH Research Grant R01 HL-39286.