The interplay between integrins αMβ2 and α5β1 during cell migration to fibronectin

Valeryi K. Lishko, Valentin P. Yakubenko, Tatiana P. Ugarova

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

A directed migration of leukocytes through the extracellular matrix requires the regulated engagement of integrin cell adhesion receptors. The integrin αMβ2 (CD11b/CD18, Mac-1) is progressively upregulated to high levels on migrating phagocytic leukocytes in response to inflammatory stimuli and is able to bind numerous ligands in the interstitial matrix. The role of αMβ2 in migration of leukocytes through the extracellular matrix and its cooperation with other leukocyte integrins during migration are not understood. Using a model system consisting of cells that express different levels of αMβ2 and an invariable level of endogenous integrin α5β1, we have explored a situation relevant to migrating neutrophils when αMβ2 and α5β1 engage the same ligand, fibronectin. We show that fibronectin is a ligand for αMβ2 and that both αMβ2 and α5β1 on the αMβ2-expressing cells contribute to adhesion to fibronectin. However, migration of these cells to fibronectin is mediated by α5β1, whereas αMβ2 retards migration. The decrease in migration correlates directly with the increased αMβ2 density. Ligation of αMβ2 with function-blocking antibodies can reverse this effect. The restorative effects of antibodies are caused by the removal of restraint imposed by the excess of αMβ2-fibronectin adhesive bonds. These findings indicate that αMβ2 can increase general cell adhesiveness which results in braking of cell migration mediated by integrin α5β1. Because αMβ2 binds numerous proteins in the extracellular matrix with a specificity overlapping that of the β1 integrins, the results suggest that αMβ2 can affect the β1 integrin-mediated cell migration.

Original languageEnglish (US)
Pages (from-to)116-126
Number of pages11
JournalExperimental Cell Research
Volume283
Issue number1
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

Keywords

  • Adhesion
  • Adhesion molecules
  • CD11b/CD18
  • Fibronectin
  • Integrins
  • Leukocytes
  • Migration

ASJC Scopus subject areas

  • Cell Biology

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