Degradation of glycosaminoglycans and fibronectin on endotoxin-stimulated endothelium by adherent neutrophils: relationship to CD11b/CD18 and L-selectin expression.
Vascular endothelial injury observed in overwhelming sepsis may be caused by neutrophil-derived enzymes. Adherence to the endothelium, a prerequisite for this process, is mediated sequentially by the neutrophil adhesion molecules L-selectin and the beta 2 integrins including CD11b/CD18. The relationship between expression of these molecules, neutrophil adherence, endothelial activation, and consequent endothelial injury was assessed by changes in heparan sulfate and fibronectin matrices. Endothelial prestimulation with lipopolysaccharide caused both an increase in adherence and a generalized reduction in heparan sulfate; disruption of the fibronectin matrix occurred only on the further addition of FMLP. Although maximal disruption of these matrices was associated with elevation of neutrophil CD11b/CD18 and reduction in L-selectin expression, these changes did not determine either the nature or extent of endothelial damage. This model may provide further insights into the interrelationship between neutrophil activation and endothelial damage in gram-negative sepsis.
Klein
N J
NJ
Department of Paediatrics, St. Mary's Hospital Medical School, London, United Kingdom.
Levin
M
M
Strobel
S
S
Finn
A
A
D015703:Antigens, CD / Q000378:metabolism*; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D019041:L-Selectin; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000502:physiology
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D006025:Glycosaminoglycans; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D019041:L-Selectin