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Molecular mechanisms of monocyte adhesion to interleukin-1beta- stimulated
endothelial cells under physiologic flow conditions
S Kukreti, K Konstantopoulos, CW Smith and LV McIntire
Cox Laboratory for Biomedical Engineering, Rice University, Houston, TX
77251-1892, USA.
This study identifies multiple pathways used by monocytes to adhere to
4-hour interleukin-1beta stimulated human umbilical vein endothelial cells
under flow conditions. Physiologic shear stresses were simulated in a flow
chamber with parallel plate geometry; quantitation of primary adhesion,
secondary adhesion, and transmigration was performed using phase contrast
videomicroscopy. Neuraminidase treatment of monocytes reduced primary
interaction by 50%, whereas blocking L-selectin or very late antigen-4
showed significant but smaller effects (approximately 30% inhibition).
However, a combined treatment against all three pathways was able to reduce
interaction by 80%. Blocking beta2 and alpha4 integrin pathways together
inhibited secondary/firm adhesion by 75%. Only 40% of firmly adherent
monocytes transmigrated across the endothelial monolayer with significantly
increased transmigration times when both beta2 and alpha4 integrins were
blocked. These results demonstrate that monocytes can use multiple
receptors to interact with endothelial cells at both primary and secondary
adhesion stages, and that these pathways have to be blocked simultaneously
for maximum inhibition.
Volume 89,
Issue 11,
pp. 4104-4111,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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