A role for the αvβ3 integrin in the transmigration of monocytes

The beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) are important for monocyte migration through inflammatory endothelium. Here we demonstrate that the integrin alpha v beta 3 is also a key player in this process. In an in vitro transendothelial migration assay, monocytes lacking beta 3 integrins revealed weak migratory ability, whereas monocytes expressing beta 3 integrins engaged in stronger migration. This migration could be partially blocked by antibodies against the integrin chains alpha L, beta 2, alpha v, or IAP, a protein functionally associated with alpha v beta 3 integrin. Transfection of beta 3 integrin chain cDNA into monocytes lacking beta 3 integrins resulted in expression of the alpha v beta 3 integrin and conferred on these cells an enhanced ability to transmigrate through cell monolayers expressing ICAM-1. These monocytes also engaged in alpha L beta 2-dependent locomotion on recombinant ICAM-1 which was enhanced by alpha v beta 3 integrin occupancy. Antibodies against IAP were able to revert this alpha v beta 3 integrin-dependent cell locomotion to control levels. Finally, adhesion assays revealed that occupancy of alpha v beta 3 integrin could decrease monocyte binding to ICAM-1. In conclusion, we show that alpha v beta 3 integrin modulates alpha L beta 2 integrin-dependent monocyte adhesion to and migration on ICAM-1. This could represent a novel mechanism to promote monocyte motility on vascular ICAM-1 and initiate subsequent transendothelial migration.