Endothelial cell glycocalyx modulates immobilization of leukocytes at the endothelial surface.
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.


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 microm 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 microm). 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 microm, 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.
Constantinescu
Alina A
AA
Department of Medical Physics, University of Amsterdam, Amsterdam, The Netherlands.
Vink
Hans
H
Spaan
Jos A E
JA
D000009:Abdominal Muscles / Q000098:blood supply; D000818:Animals; D002196:Capillaries / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D019276:Glycocalyx / Q000502:physiology*; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D010477:Perfusion; D011133:Polysaccharide-Lyases / Q000008:administration & dosage / Q000494:pharmacology
D006493:Heparin; D006497:Heparan Sulfate; D008077:Lipoproteins, LDL; D011133:Polysaccharide-Lyases; C099252:oxidized low density lipoprotein; C021349:heparitinsulfate lyase