The leukocyte integrin α(D)β2 binds VCAM-1: Evidence for a binding interface between I domain and VCAM-1

Monica Van Der Vieren, David T. Crowe, Denise Hoekstra, Rosemay Vazeux, Patricia A. Hoffman, Mitchell H. Grayson, Bruce S. Bochner, W. Michael Gallatin, Donald E. Staunton*

*Corresponding author for this work

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

The trafficking of leukocytes through tissues is supported by an interaction between the β2 (CD18) integrins CD11a/CDl8 (LFA-1) and CD11b/CD18 (Mac-1) and their ligand ICAM-1. The most recently identified and fourth member of the β2 integrins, α(D)β2, selectively binds ICAM-3 and does not appear to bind ICAM-1. We have reported recently that α(D)β2 can support eosinophil adhesion to VCAM-1. Here we demonstrate that expression of α(D)β2 in a lymphoid cell that does not express α4 integrins confers efficient binding to VCAM-1. In addition, a soluble form of α(D)β2 binds VCAM-1 with greater efficiency relative to ICAM-3. The I domain of αD contains a binding site for VCAM-1 since recombinant α(D) I domain binds specifically to VCAM-1. In addition, α(D) mAb that block cellular binding to VCAM-1 bind the α(D) I domain. Using VCAM-1 mutants we have determined that the binding site on VCAM-1 for α(D)β2 overlaps with that of α4 integrins. Substitution of VCAM-1 aspartate at position 40, D40, within the conserved integrin binding site, diminishes binding to α(D)β2 and abrogates binding to the α(D) I domain. The corresponding integrin binding site residue in ICAM-3 is also essential to α(D)β2 binding. Finally, we demonstrate that α(D)β2 can support lymphoid cell adhesion to VCAM-1 under flow conditions at levels equivalent to those mediated by α4β1. These results indicate that VCAM-1 can bind to an I domain and that the binding of α(D)β2 to VCAM-1 may contribute to the trafficking of a subpopulation of leukocytes that express α(D)β2.

Original languageEnglish (US)
Pages (from-to)1984-1990
Number of pages7
JournalJournal of Immunology
Volume163
Issue number4
StatePublished - Aug 15 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Van Der Vieren, M., Crowe, D. T., Hoekstra, D., Vazeux, R., Hoffman, P. A., Grayson, M. H., Bochner, B. S., Gallatin, W. M., & Staunton, D. E. (1999). The leukocyte integrin α(D)β2 binds VCAM-1: Evidence for a binding interface between I domain and VCAM-1. Journal of Immunology, 163(4), 1984-1990.