Published online before print July 10, 2003, doi: 10.1161/01.ATV.0000085630.24353.3D
© 2003 American Heart Association, Inc.
Vascular Biology |
Endothelial Cell Glycocalyx Modulates Immobilization of Leukocytes at the Endothelial Surface
From the Department of Medical Physics, University of Amsterdam, Amsterdam, The Netherlands.
Correspondence to Hans Vink, PhD, Department of Medical Physics, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, Netherlands. E-mail h.vink{at}amc.uva.nl
Objective— A thick endothelial glycocalyx provides the endothelial surface with a nonadherent shield. Oxidized LDL (Ox-LDL) degrades the endothelial glycocalyx. We hypothesized that glycocalyx degradation stimulates leukocyte-endothelial cell adhesion, whereas intravascular supplementation with sulfated polysaccharides reconstitutes the endothelial glycocalyx and attenuates Ox-LDL-induced leukocyte-endothelial cell adhesion.
Methods and Results— Degradation of the endothelial glycocalyx by local microinjection of heparitinase (10 to 50 U/mL) into mouse cremaster venules dose-dependently increased the number of adherent leukocytes. Systemic administration of Ox-LDL (0.4 mg/100 g body weight) induced 10.1±0.9 adherent leukocytes/100 µm at 60 minutes. In the venules perfused with 500-kDa dextran sulfate (1 mg/mL), the number of adherent leukocytes at 60 minutes after Ox-LDL bolus application was not influenced (9.2±1.0 leukocytes/100 µm). However, the venules locally perfused with heparan sulfate (10 mg/mL) or heparin (1 mg/mL) displayed a significantly lower number of adherent leukocytes induced by Ox-LDL: 5.1±0.7 and 5.4±0.9 leukocytes/100 µm, respectively (P<0.05). Fluorescently labeled heparan sulfate and heparin, but not dextran sulfate, attached to the venule luminal surface after Ox-LDL administration.
Conclusions— Endothelial glycocalyx degradation stimulates leukocyte immobilization at the endothelial surface. Circulating heparan sulfate and heparin attach to the venule wall and attenuate Ox-LDL-induced leukocyte immobilization.
Key Words: glycocalyx • leukocytes • oxidized LDL • heparin
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