The role of integrin αDβ2 (CD11d/CD18) in monocyte/macrophage migration

Valentin P. Yakubenko, Nataly Belevych, Daria Mishchuk, Aleksey Schurin, Stephen C T Lam, Tatiana Ugarova

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Integrin αDβ2 (CD11d/CD18) is a multiligand macrophage receptor with recognition specificity identical to that of the major myeloid cell-specific integrin αMβ2 (CD11b/CD18, Mac-1). Despite its prominent upregulation on inflammatory macrophages, the role of αDβ2 in monocyte and macrophage migration is unknown. In this study, we have generated model and natural cell lines expressing different densities of αDβ2 and examined their migration to various extracellular matrix proteins. When expressed at a low density, αDβ2 on the surface of recombinant HEK293 cells and murine IC-21 macrophages cooperates with β13 integrins to support cell migration. However, its increased expression on the αDβ2-expressing HEK293 cells and its upregulation by PMA on the IC-21 macrophages result in increased cell adhesiveness and inhibition of cell migration. Furthermore, ligation of αDβ2 with anti-αD blocking antibodies restores β13-driven cell migration by removing the excess αDβ2-mediated adhesive bonds. Consistent with in vitro data, increased numbers of inflammatory macrophages were recovered from the inflamed peritoneum of mice after the administration of anti-αD antibody. These results demonstrate that the density of αDβ2 is critically involved in modulating macrophage adhesiveness and their migration, and suggest that low levels of αDβ2 contribute to monocyte migration while αDβ2 upregulation on differentiated macrophages may facilitate their retention at sites of inflammation.

Original languageEnglish (US)
Pages (from-to)2569-2578
Number of pages10
JournalExperimental Cell Research
Volume314
Issue number14
DOIs
StatePublished - Aug 15 2008

Keywords

  • CD11d/CD18
  • Cell migration
  • Inflammation
  • Integrin αβ
  • Macrophage

ASJC Scopus subject areas

  • Cell Biology

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    Yakubenko, V. P., Belevych, N., Mishchuk, D., Schurin, A., Lam, S. C. T., & Ugarova, T. (2008). The role of integrin αDβ2 (CD11d/CD18) in monocyte/macrophage migration. Experimental Cell Research, 314(14), 2569-2578. https://doi.org/10.1016/j.yexcr.2008.05.016