Faculty Collaboration Database

The leukocyte integrin alpha D beta 2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1. J Immunol 1999 Aug 15;163(4):1984-90

Date

08/10/1999

Pubmed ID

10438935

Scopus ID

2-s2.0-0033566675 (requires institutional sign-in at Scopus site)   94 Citations

Abstract

The trafficking of leukocytes through tissues is supported by an interaction between the beta 2 (CD18) integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1) and their ligand ICAM-1. The most recently identified and fourth member of the beta 2 integrins, alpha D beta 2, selectively binds ICAM-3 and does not appear to bind ICAM-1. We have reported recently that alpha D beta 2 can support eosinophil adhesion to VCAM-1. Here we demonstrate that expression of alpha D beta 2 in a lymphoid cell that does not express alpha 4 integrins confers efficient binding to VCAM-1. In addition, a soluble form of alpha D beta 2 binds VCAM-1 with greater efficiency relative to ICAM-3. The I domain of alpha D contains a binding site for VCAM-1 since recombinant alpha D I domain binds specifically to VCAM-1. In addition, alpha D mAb that block cellular binding to VCAM-1 bind the alpha D I domain. Using VCAM-1 mutants we have determined that the binding site on VCAM-1 for alpha D beta 2 overlaps with that of alpha 4++ integrins. Substitution of VCAM-1 aspartate at position 40, D40, within the conserved integrin binding site, diminishes binding to alpha D beta 2 and abrogates binding to the alpha D I domain. The corresponding integrin binding site residue in ICAM-3 is also essential to alpha D beta 2 binding. Finally, we demonstrate that alpha D beta 2 can support lymphoid cell adhesion to VCAM-1 under flow conditions at levels equivalent to those mediated by alpha 4 beta 1. These results indicate that VCAM-1 can bind to an I domain and that the binding of alpha D beta 2 to VCAM-1 may contribute to the trafficking of a subpopulation of leukocytes that express alpha D beta 2.

Author List

Van der Vieren M, Crowe DT, Hoekstra D, Vazeux R, Hoffman PA, Grayson MH, Bochner BS, Gallatin WM, Staunton DE

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Blocking
Antibodies, Monoclonal
Antigens, CD
Binding Sites
Binding Sites, Antibody
CD11 Antigens
Cell Adhesion
Cell Movement
Humans
Integrin alpha Chains
Integrin alpha4
Integrins
Jurkat Cells
Leukocytes
Mice
Mice, Inbred BALB C
Peptide Fragments
Protein Binding
Receptors, Cytoadhesin
Recombinant Proteins
Rheology
Vascular Cell Adhesion Molecule-1