Increased leukocyte-endothelial interactions in syndecan-1-deficient mice involve heparan sulfate-dependent and -independent steps.
OBJECTIVE
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.
Götte
Martin
M
Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Bernfield
Merton
M
Joussen
Antonia M
AM
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011509:Proteoglycans / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D053668:Syndecan-1; D053667:Syndecans; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D006493:Heparin; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D053668:Syndecan-1; D053667:Syndecans; D014409:Tumor Necrosis Factor-alpha; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse