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A role for the alpha v beta 3 integrin in the transmigration of monocytes
Author(s): Weerasinghe D, McHugh KP, Ross FP, Brown EJ, Gisler RH, Imhof BA
Source: JOURNAL OF CELL BIOLOGY    Volume: 142    Issue: 2    Pages: 595-607    Published: JUL 27 1998  
Times Cited: 78     References: 76     
Abstract: 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.

Document Type: Article
Language: English
Reprint Address: Imhof, BA (reprint author), Univ Geneva, Dept Pathol, 1 Rue Michel Servet, CH-1211 Geneva, Switzerland
Addresses:
1. Ctr Med Univ Geneva, Dept Pathol, CH-1211 Geneva, Switzerland
2. Washington Univ, Med Ctr, Dept Internal Med, St Louis, MO 63110 USA
3. Washington Univ, Med Ctr, Dept Pathol, St Louis, MO 63110 USA
4. Basel Inst Immunol, CH-4005 Basel, Switzerland
Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
Subject Category: Cell Biology
IDS Number: 106CC
ISSN: 0021-9525
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