CD137 enhances monocyte–ICAM-1 interactions in an E-selectin-dependent manner under flow conditions

Expression of CD137, a member of the tumor necrosis factor receptor family, is inducible on vascular endothelial cells by proinflammatory stimuli. Its ligand is expressed as a transmembrane protein on the surface of monocytes, and transmits activating signals into monocytes (reverse signaling) inducing monocyte migration. These findings led to the hypothesis that CD137 expression on activated endothelial cells facilitates recruitment of monocytes into inflammatory tissues including atherosclerotic lesions. Data from this study demonstrate that CD137 expression is inducible on endothelial cells by TNF stimulation. Recombinant CD137 protein and CD137 expressed on activated endothelial cells enhance ICAM-1-mediated adhesion of monocytes under defined flow conditions in vitro. CD137 seems not to play a role in tethering of monocytes since this activity is completely E-selectin-dependent. In addition, LFA-1 affinity and clustering on monocytic cells is enhanced by CD137. In summary, CD137 expression is induced on vascular endothelial cells by proinflammatory mediators and strengthens ICAM-1 and LFA-1-mediated adhesion of monocytes. These data support a role for CD137 in the recruitment of monocytes to inflammatory tissues.