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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.JI

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.

Authors+Show Affiliations

ICOS Corp., Bothell, WA 98021, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10438935

Citation

Van der Vieren, M, et al. "The Leukocyte Integrin Alpha D Beta 2 Binds VCAM-1: Evidence for a Binding Interface Between I Domain and VCAM-1." Journal of Immunology (Baltimore, Md. : 1950), vol. 163, no. 4, 1999, pp. 1984-90.
Van der Vieren M, Crowe DT, Hoekstra D, et al. The leukocyte integrin alpha D beta 2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1. J Immunol. 1999;163(4):1984-90.
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 alpha D beta 2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1. Journal of Immunology (Baltimore, Md. : 1950), 163(4), 1984-90.
Van der Vieren M, et al. 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. PubMed PMID: 10438935.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The leukocyte integrin alpha D beta 2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1. AU - Van der Vieren,M, AU - Crowe,D T, AU - Hoekstra,D, AU - Vazeux,R, AU - Hoffman,P A, AU - Grayson,M H, AU - Bochner,B S, AU - Gallatin,W M, AU - Staunton,D E, PY - 1999/8/10/pubmed PY - 1999/8/10/medline PY - 1999/8/10/entrez SP - 1984 EP - 90 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 163 IS - 4 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10438935/The_leukocyte_integrin_alpha_D_beta_2_binds_VCAM_1:_evidence_for_a_binding_interface_between_I_domain_and_VCAM_1_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10438935 DB - PRIME DP - Unbound Medicine ER -