Characterization of the hepatic endothelial glycocalyx of sialidase deficient mice in response to TNFα

Evidence exists that components of the venular glycocalyx are shed and sialic acid is cleaved during inflammation. The objective of this study was to examine the role of sialidase in altering the hepatic glycocalyx. Female C57Bl/6 (WT) or sialidase deficient (B6Sm −/− ) mice were injected with 500 ng of TNFα or saline and the hepatic microcirculation examined by intravital confocal microscopy at 4h. Sugars present on the vasculature were detected by IV injection of FITC‐labeled Bandeiraea simplicifolia (BS‐1) (detects α‐ N ‐acetylgalactosamine and α‐galactose residues) or Texas‐Red‐labeled Lycopersicon esculentum (TL) (detects N ‐acetylglucosamine residues). Both lectins labeled the sinusoidal endothelium with no significant difference between the groups in the mean fluorescence intensity of the BS‐1 or TLlabeled glycocalyx. However, the saline treated WT mice had a thicker glycocalyx as compared to the saline treated B6Sm −/− mice (876 ±37 nm and 777 ± 18 nm, respectively) and TNFα stimulation resulted in a decrease of the glycocalyx thickness (772 ± 45 nm and 658 ± 23 nm, respectively). Our data supports the idea that components of the glycocalyx are shed during inflammation resulting in loss of glycocalyx height. Surprisingly, these sugars were expressed primarily on the sinusoids rather than venules and in contrast to other vascular beds, were not removed during TNFα‐induced hepatic inflammation.