Increased leukocyte-endothelial interactions in syndecan-1-deficient mice involve heparan sulfate-dependent and -independent steps

Purpose: Increased leukocyte-endothelial interactions and angiogenesis are observed in the ocular vasculature of mice lacking the cell surface heparan sulfate proteoglycan syndecan-1. Here we investigate the interaction of defined leukocyte populations of syndecan-1 knockout (KO) and wild- type mice with endothelial cells in vitro. Heparin is used to substitute for the lack of syndecan-1 heparan sulfate. Methods: The adhesion of polymorphonuclear cells and monocytes purified from syndecan-1 KO and wild-type mice to unstimulated and TNF-alpha-treated human umbilical vein endothelial cells (HUVECs) was measured in a static adhesion assay. Results: Adhesion of syndecan-1 KO leukocytes to HUVECs is increased relative to wild- type leukocytes, being more pronounced in TNF-alpha-stimulated HUVECs. Heparin reverted this adhesion to wild-type levels in unstimulated endothelium. Conclusions: Syndecan-1 acts as a negative regulator of polymorphonuclear leukocytes (PMNs) and monocyte adhesion to endothelial cells. Its heparan sulfate chains play different roles in this process in unstimulated endothelia compared to TNF-alpha-stimulated endothelia.