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J. Cell Biol., Volume 142, Number 2, July 27, 1998 595-607

A Role for the alpha vbeta 3 Integrin in the Transmigration of Monocytes

Dheepika Weerasinghe,* Kevin P. McHugh,Dagger Frederick P. Ross,Dagger Eric J. Brown,§ Roland H. Gisler,* and Beat A. Imhof*parallel

* Basel Institute for Immunology, CH-4005 Basel, Switzerland; Dagger  Department of Pathology, and § Department of Internal Medicine, Washington University Medical Centre, St. Louis, Missouri 63110; and parallel  Department of Pathology, Centre Médical Universitaire, CH-1211 Geneva, Switzerland

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 vbeta 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 vbeta 3 integrin. Transfection of beta 3 integrin chain cDNA into monocytes lacking beta 3 integrins resulted in expression of the alpha vbeta 3 integrin and conferred on these cells an enhanced ability to transmigrate through cell monolayers expressing ICAM-1. These monocytes also engaged in alpha Lbeta 2-dependent locomotion on recombinant ICAM-1 which was enhanced by alpha vbeta 3 integrin occupancy. Antibodies against IAP were able to revert this alpha vbeta 3 integrin-dependent cell locomotion to control levels. Finally, adhesion assays revealed that occupancy of alpha vbeta 3 integrin could decrease monocyte binding to ICAM-1.

In conclusion, we show that alpha vbeta 3 integrin modulates alpha Lbeta 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.

Key words: monocytealpha vbeta 3 integrinalpha Lbeta 2 integrinmigrationICAM-1


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