MOLECULAR MECHANISMS OF MONOCYTE ADHESION TO INTERLEUKIN-1-BETA-STIMULATED ENDOTHELIAL-CELLS UNDER PHYSIOLOGICAL FLOW CONDITIONS

This study identifies multiple pathways used by monocytes to adhere to 4-hour interleukin-1 beta stimulated human umbilical vein endothelial cells under flow conditions, Physiologic shear stresses were simulate d in a flow chamber with parallel plate geometry; quantitation of prim ary adhesion, secondary adhesion, and transmigration was performed usi ng phase contrast videomicroscopy. Neuraminidase treatment of monocyte s reduced primary interaction by 50%, whereas blocking L-selectin or v ery late antigen-4 showed significant but smaller effects (similar to 30% inhibition), However, a combined treatment against all three pathw ays was able to reduce interaction by 80%, Blocking beta(2) and alpha( 4) integrin pathways together inhibited secondary/firm adhesion by 75% . Only 40% of firmly adherent monocytes transmigrated across the endot helial monolayer with significantly increased transmigration times whe n both beta(2) and alpha(4) integrins were blocked. These results demo nstrate that monocytes can use multiple receptors to interact with end othelial cells at both primary and secondary adhesion stages, and that these pathways have to be blocked simultaneously for maximum inhibiti on. (C) 1997 by The American Society of Hematology.