The highly sialoglycosylated extracellular domain of podocalyxin (Podxl) is a constituent of the endothelial glycocalyx of most blood vessels but it is unknown if Podxl plays a prominent role in the function of the glycocalyx as a regulator of leukocyte-endothelial adhesion. We have recently found that mice lacking Podxl in the vascular endothelium develop histological lesions compatible with severe vasculitis resulting in organ failure and premature death. In this work, we show that these mice have an increased quantity of resident leukocytes within the peritoneal cavity in both basal and inflammatory conditions. Adhesion of macrophagic cells to lung endothelial cells from Podxl-deficient mice was increased under inflammatory stimuli. Both, chemokine binding and chemokine-mediated adhesion of immune cells were significantly higher in Podxl-deficient endothelial cells. Moreover, glycocalyx function assessed by measuring the anticoagulant capacity of endothelial cell monolayers to inactivate thrombin was significantly altered in the absence of Podxl. Overall, the results suggest that Podxl is an essential component of the glycocalyx and has an important so far unknown role in preventing leukocyte-endothelial cell adhesion under resting and inflammatory conditions.
Keywords: Endothelial cell; Glycocalyx; Inflammation; Leukocyte-endothelial cell adhesion; Podocalyxin.
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