Integrin in the Transmigration of Monocytes

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