HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Van der Vieren, M. Articles by Staunton, D. E. Search for Related Content PubMed PubMed Citation Articles by Van der Vieren, M. Articles by Staunton, D. E.

The Leukocyte Integrin _Dß₂ 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^* and Donald E. Staunton^1,*

^* ICOS Corp., Bothell, WA 98021; and Department of Medicine, Division of Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21218

The trafficking of leukocytes through tissues is supported by an interaction between the ß₂ (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 ß₂ integrins, _Dß₂, selectively binds ICAM-3 and does not appear to bind ICAM-1. We have reported recently that _Dß₂ can support eosinophil adhesion to VCAM-1. Here we demonstrate that expression of _Dß₂ in a lymphoid cell that does not express ₄ integrins confers efficient binding to VCAM-1. In addition, a soluble form of _Dß₂ binds VCAM-1 with greater efficiency relative to ICAM-3. The I domain of D contains a binding site for VCAM-1 since recombinant _D I domain binds specifically to VCAM-1. In addition, _D mAb that block cellular binding to VCAM-1 bind the _D I domain. Using VCAM-1 mutants we have determined that the binding site on VCAM-1 for _Dß₂ overlaps with that of ₄ integrins. Substitution of VCAM-1 aspartate at position 40, D40, within the conserved integrin binding site, diminishes binding to _Dß₂ and abrogates binding to the _D I domain. The corresponding integrin binding site residue in ICAM-3 is also essential to _Dß₂ binding. Finally, we demonstrate that _Dß₂ can support lymphoid cell adhesion to VCAM-1 under flow conditions at levels equivalent to those mediated by ₄ß₁. These results indicate that VCAM-1 can bind to an I domain and that the binding of _Dß₂ to VCAM-1 may contribute to the trafficking of a subpopulation of leukocytes that express _Dß₂.

This article has been cited by other articles:

				Y. Miyazaki, M. Bunting, D. M. Stafforini, E. S. Harris, T. M. McIntyre, S. M. Prescott, V. S. Frutuoso, F. C. Amendoeira, D. de Oliveira Nascimento, A. Vieira-de-Abreu, et al. Integrin {alpha}D 2 Is Dynamically Expressed by Inflamed Macrophages and Alters the Natural History of Lethal Systemic Infections J. Immunol., January 1, 2008; 180(1): 590 - 600. [Abstract] [Full Text] [PDF]

				C. Sadhu, H. J. Ting, B. Lipsky, K. Hensley, L. F. Garcia-Martinez, S. I. Simon, and D. E. Staunton CD11c/CD18: novel ligands and a role in delayed-type hypersensitivity J. Leukoc. Biol., June 1, 2007; 81(6): 1395 - 1403. [Abstract] [Full Text] [PDF]

				S. R. Barthel, D. S. Annis, D. F. Mosher, and M. W. Johansson Differential Engagement of Modules 1 and 4 of Vascular Cell Adhesion Molecule-1 (CD106) by Integrins {alpha}4beta1 (CD49d/29) and {alpha}Mbeta2 (CD11b/18) of Eosinophils J. Biol. Chem., October 27, 2006; 281(43): 32175 - 32187. [Abstract] [Full Text] [PDF]

				V. P. Yakubenko, S. P. Yadav, and T. P. Ugarova Integrin {alpha}Dbeta2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties Blood, February 15, 2006; 107(4): 1643 - 1650. [Abstract] [Full Text] [PDF]

				S. G. Kallapur, T. J. M. Moss, M. Ikegami, R. L. Jasman, J. P. Newnham, and A. H. Jobe Recruited Inflammatory Cells Mediate Endotoxin-induced Lung Maturation in Preterm Fetal Lambs Am. J. Respir. Crit. Care Med., November 15, 2005; 172(10): 1315 - 1321. [Abstract] [Full Text] [PDF]

				T. Ulyanova, L. M. Scott, G. V. Priestley, Y. Jiang, B. Nakamoto, P. A. Koni, and T. Papayannopoulou VCAM-1 expression in adult hematopoietic and nonhematopoietic cells is controlled by tissue-inductive signals and reflects their developmental origin Blood, July 1, 2005; 106(1): 86 - 94. [Abstract] [Full Text] [PDF]

				M. A. Oatway, Y. Chen, J. C. Bruce, G. A. Dekaban, and L. C. Weaver Anti-CD11d Integrin Antibody Treatment Restores Normal Serotonergic Projections to the Dorsal, Intermediate, and Ventral Horns of the Injured Spinal Cord J. Neurosci., January 19, 2005; 25(3): 637 - 647. [Abstract] [Full Text] [PDF]

				H. Wu, J. R. Rodgers, X.-Y. D. Perrard, J. L. Perrard, J. E. Prince, Y. Abe, B. K. Davis, G. Dietsch, C. W. Smith, and C. M. Ballantyne Deficiency of CD11b or CD11d Results in Reduced Staphylococcal Enterotoxin-Induced T Cell Response and T Cell Phenotypic Changes J. Immunol., July 1, 2004; 173(1): 297 - 306. [Abstract] [Full Text] [PDF]

				D. Gris, D. R. Marsh, M. A. Oatway, Y. Chen, E. F. Hamilton, G. A. Dekaban, and L. C. Weaver Transient Blockade of the CD11d/CD18 Integrin Reduces Secondary Damage after Spinal Cord Injury, Improving Sensory, Autonomic, and Motor Function J. Neurosci., April 21, 2004; 24(16): 4043 - 4051. [Abstract] [Full Text] [PDF]

				E. P. Moiseeva Adhesion receptors of vascular smooth muscle cells and their functions Cardiovasc Res, December 1, 2001; 52(3): 372 - 386. [Abstract] [Full Text] [PDF]

				T. Papayannopoulou, G. V. Priestley, B. Nakamoto, V. Zafiropoulos, and L. M. Scott Molecular pathways in bone marrow homing: dominant role of {alpha}4{beta}1 over {beta}2-integrins and selectins Blood, October 15, 2001; 98(8): 2403 - 2411. [Abstract] [Full Text] [PDF]

				E. B. Carson-Walter, D. N. Watkins, A. Nanda, B. Vogelstein, K. W. Kinzler, and B. St. Croix Cell Surface Tumor Endothelial Markers Are Conserved in Mice and Humans Cancer Res., September 1, 2001; 61(18): 6649 - 6655. [Abstract] [Full Text] [PDF]

				D. Bouvard, C. Brakebusch, E. Gustafsson, A. Aszodi, T. Bengtsson, A. Berna, and R. Fassler Functional Consequences of Integrin Gene Mutations in Mice Circ. Res., July 30, 2001; 89(3): 211 - 223. [Abstract] [Full Text] [PDF]

				P. A. Koni, S. K. Joshi, U.-A. Temann, D. Olson, L. Burkly, and R. A. Flavell Conditional Vascular Cell Adhesion Molecule 1 Deletion in Mice: Impaired Lymphocyte Migration to Bone Marrow J. Exp. Med., March 19, 2001; 193(6): 741 - 754. [Abstract] [Full Text] [PDF]

				J. G. Wagner and R. A. Roth Neutrophil Migration Mechanisms, with an Emphasis on the Pulmonary Vasculature Pharmacol. Rev., September 1, 2000; 52(3): 349 - 374. [Abstract] [Full Text] [PDF]

				H. Tachimoto, M. M. Burdick, S. A. Hudson, M. Kikuchi, K. Konstantopoulos, and B. S. Bochner CCR3-Active Chemokines Promote Rapid Detachment of Eosinophils from VCAM-1 In Vitro J. Immunol., September 1, 2000; 165(5): 2748 - 2754. [Abstract] [Full Text] [PDF]

				J. M. G. Higgins, M. Cernadas, K. Tan, A. Irie, J.-h. Wang, Y. Takada, and M. B. Brenner The Role of alpha and beta Chains in Ligand Recognition by beta 7 Integrins J. Biol. Chem., August 11, 2000; 275(33): 25652 - 25664. [Abstract] [Full Text] [PDF]

				E. S. Harris, T. M. McIntyre, S. M. Prescott, and G. A. Zimmerman The Leukocyte Integrins J. Biol. Chem., July 28, 2000; 275(31): 23409 - 23412. [Full Text] [PDF]