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© The Rockefeller University Press, 0021-9525/1998//595 $5.00
The Journal of Cell Biology, Volume 142, Number 2, , 1998 595-607


Articles

A Role for the {alpha}vβ3 Integrin in the Transmigration of Monocytes



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

* Basel Institute for Immunology, CH-4005 Basel, Switzerland; {ddagger} 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 β2 integrins and intercellular adhesion molecule-1 (ICAM-1) are important for monocyte migration through inflammatory endothelium. Here we demonstrate that the integrin {alpha}vβ3 is also a key player in this process. In an in vitro transendothelial migration assay, monocytes lacking β3 integrins revealed weak migratory ability, whereas monocytes expressing β3 integrins engaged in stronger migration. This migration could be partially blocked by antibodies against the integrin chains {alpha}L, β2, {alpha}v, or IAP, a protein functionally associated with {alpha}vβ3 integrin. Transfection of β3 integrin chain cDNA into monocytes lacking β3 integrins resulted in expression of the {alpha}vβ3 integrin and conferred on these cells an enhanced ability to transmigrate through cell monolayers expressing ICAM-1. These monocytes also engaged in {alpha}Lβ2-dependent locomotion on recombinant ICAM-1 which was enhanced by {alpha}vβ3 integrin occupancy. Antibodies against IAP were able to revert this {alpha}vβ3 integrin-dependent cell locomotion to control levels. Finally, adhesion assays revealed that occupancy of {alpha}vβ3 integrin could decrease monocyte binding to ICAM-1.

In conclusion, we show that {alpha}vβ3 integrin modulates {alpha}Lβ2 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: monocyte • {alpha}vβ3 integrin • {alpha}Lβ2 integrin • migration • ICAM-1



Abbreviations used in this paper: ECM, extracellular matrix; GM-CSF, granulocyte macrophage colony-stimulating factor; HUVEC, human umbilical vein endothelial cells; IAP, integrin-associated protein; ICAM-1, intercellular adhesion molecule-1; IMDM, Iscove's modified Dulbecco's medium; MCP-1, monocyte chemoattractant protein-1; MHC, major histocompatibility complex; PECAM-1, platelet endothelial cell adhesion molecule-1; TEM, transendothelial migration; VCAM-1, vascular cell adhesion molecule-1.

Address all correspondence to Beat A. Imhof, Professor of Pathology, Geneva University, Department of Pathology, 1, rue Michel-Servet, CH-1211 Geneva, Switzerland. Tel.: (41) 22-702-57-47. Fax: (41) 22-702-57-46. E-mail: beat.imhof{at}medecine.unige.ch



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