MONOCYTES USE EITHER CD11 CD18 OR VLA-4 TO MIGRATE ACROSS HUMAN ENDOTHELIUM IN-VITRO/

Monocytes traverse the endothelial lining of blood vessels and migrate into both normal and inflamed tissues. An in vitro model of a vascula r wall, consisting of HUVEC cultured on acellular human amniotic tissu e, was employed to examine the roles of several adhesion molecules in diapedesis of monocytes. Approximately half of the monocytes added to this system traversed the endothelium in a time-dependent fashion, com pleting their migration within 2 h. Pretreatment of HUVEC with IL-1 be ta for 4 h increased the rate of adhesion of monocytes, but did not al ter the number that ultimately migrated. A mAb to CD18, ts1/18, greatl y inhibited adhesion and migration of monocytes when the monocytes wer e incubated with unstimulated HUVEC monolayers for 20 min. Much less i nhibition was observed when the incubation period was increased to 2 h or when HUVEC were pretreated with IL-1 beta. A mAb to VLA-4, HP1/2, had little or no inhibitory effect in all cases. The combination of ts 1/18 and HP1/2 greatly inhibited (up to 98%) adhesion and migration of monocytes across both unstimulated and IL-1 beta-stimulated monolayer s. Additional inhibition experiments indicated that VLA-4 interacted w ith unstimulated endothelium by binding to VCAM-1 and, to a much lesse r extent, fibronectin. These results suggest that monocytes are capabl e of interacting with endothelium during diapedesis via either CD11/CD 18- or VLA-4-dependent pathways.