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

A Role for the v3 Integrin in the Transmigration of Monocytes

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

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

The 2 integrins and intercellular adhesion molecule-1 (ICAM-1) are important for monocyte migration through inflammatory endothelium. Here we demonstrate that the integrin v3 is also a key player in this process. In an in vitro transendothelial migration assay, monocytes lacking 3 integrins revealed weak migratory ability, whereas monocytes expressing 3 integrins engaged in stronger migration. This migration could be partially blocked by antibodies against the integrin chains L, 2, v, or IAP, a protein functionally associated with v3 integrin. Transfection of 3 integrin chain cDNA into monocytes lacking 3 integrins resulted in expression of the v3 integrin and conferred on these cells an enhanced ability to transmigrate through cell monolayers expressing ICAM-1. These monocytes also engaged in L2-dependent locomotion on recombinant ICAM-1 which was enhanced by v3 integrin occupancy. Antibodies against IAP were able to revert this v3 integrin-dependent cell locomotion to control levels. Finally, adhesion assays revealed that occupancy of v3 integrin could decrease monocyte binding to ICAM-1.

In conclusion, we show that v3 integrin modulates L2 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.

monocyte;  v3 integrin;  L2 integrin;  migration;  ICAM-1

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