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M Clozel, H Kuhn and HR Baumgartner
F. Hoffman-La Roche & Co., Limited Company, Basel, Switzerland.
It has been reported that cultured endothelial cells become procoagulant
when exposed to endotoxin. This prompted us to investigate whether human
endothelial cells treated with endotoxin could promote the generation of
fibrin when exposed to human flowing blood. For this purpose we used a
parallel-plate perfusion chamber in which confluent cultured endothelial
cells from human umbilical veins were exposed for five minutes to directly
drawn human nonanticoagulated blood, at wall shear rates of 100, 650, and
2600 sec-1. Fibrin deposition was assessed by morphometry. No fibrin
deposition occurred on normal endothelial cells. In contrast, cells
incubated with endotoxin for 4 or 18 hours induced fibrin deposition, but
only at a shear rate of 100 sec-1. Since some extracellular matrix was
exposed between the cells, we investigated whether extracellular matrix
played a role in fibrin formation. When the endothelial cells incubated or
not with endotoxin were removed by EDTA, the exposed extracellular matrix
perfused with blood at 100 sec-1 supported platelet and fibrin deposition
in both cases. This suggests that the effect of endotoxin on endothelial
cells was not due to extracellular matrix alteration but only to cellular
activation or secretion of procoagulant substances. We conclude that human
endothelial cells treated with endotoxin can trigger fibrin formation and
deposition at their surface when exposed to flowing blood at low shear
rate.
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| Copyright © 1989 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
