Endotoxin-induced neutrophil adherence to endothelium: relationship to CD11b/CD18 and L-selectin expression and matrix disruption.
The injury to vascular endothelium seen in severe bacterial infection may be mediated by neutrophil-derived enzymes. Neutrophil adhesion to endothelium, a prerequisite for this process, is mediated sequentially by the leukocyte adhesion molecules L-selectin and the beta 2 integrins, including CD11b/CD18. We have explored the relationship between expression of these molecules, neutrophil adherence, endothelial activation, and consequent endothelial injury, as assessed in vitro by changes to HS and FN matrices that colocalize. Endothelial prestimulation with LPS (endotoxin) caused an increase in adherence and an inversely proportional disruption in the HS matrix; disruption of the FN matrix only occurred on the further addition of fMLP. Although maximal changes in these matrices were 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. CD11b/CD18 expression was similar in both adherent and nonadherent neutrophils, while L-selectin was shed in association with adherence in the absence of other stimuli. These changes in expression were thus independently regulated. This model may provide further insights into the interrelationship between neutrophil adhesion and activation and endothelial damage in infection with gram-negative bacteria.
Finn
A
A
Department of Paediatrics, University of Sheffield, Children's Hospital, England.
Strobel
S
S
Levin
M
M
Klein
N
N
D015703:Antigens, CD / Q000378:metabolism*; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D019041:L-Selectin; D008070:Lipopolysaccharides / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D006497:Heparan Sulfate; D019041:L-Selectin; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D009240:N-Formylmethionine Leucyl-Phenylalanine