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* Division of Hematology, the Hematology Central Laboratory of the University of Lausanne, 1011-CHUV Lausanne; and This study examines the role of L-selectin in
monocyte adhesion to arterial endothelium, a key
pathogenic event of atherosclerosis. Using a nonstatic
(rotation) adhesion assay, we observed that monocyte
binding to bovine aortic endothelium at 4°C increased four to nine times upon endothelium activation with
tumor necrosis factor (TNF)- Biomedical Engineering Laboratory of the Swiss Federal Institute of Technology, 1015-PSE-Ecublens, Switzerland
. mAb-blocking experiments demonstrated that L-selectin mediates a major
part (64 ± 18%) of monocyte attachment. Videomicroscopy experiments performed under flow indicated
that monocytes abruptly halted on 8-h TNF--activated aortic endothelium, ~80% of monocyte attachment being mediated by L-selectin. Flow cytometric
studies with a L-selectin/IgM heavy chain chimeric protein showed calcium-dependent L-selectin binding to
cytokine-activated and, unexpectedly, unactivated aortic cells. Soluble L-selectin binding was completely inhibited by anti-L-selectin mAb or by aortic
cell exposure to trypsin. Experiments with cycloheximide, chlorate, or neuraminidase showed that protein
synthesis and sulfate groups, but not sialic acid residues, were essential for L-selectin counterreceptor
function. Moreover, heparin lyases partially inhibited
soluble L-selectin binding to cytokine-activated aortic
cells, whereas a stronger inhibition was seen with unstimulated endothelial cells, suggesting that cytokine
activation could induce the expression of additional ligand(s) for L-selectin, distinct from heparan sulfate
proteoglycans. Under flow, endothelial cell treatment
with heparinase inhibited by ~80% monocyte attachment to TNF--activated aortic endothelium, indicating a major role for heparan sulfate proteoglycans in
monocyte-endothelial interactions. Thus, L-selectin
mediates monocyte attachment to activated aortic endothelium, and heparan sulfate proteoglycans serve as
arterial ligands for monocyte L-selectin.
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