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JAM-1 is a ligand of the β2 integrin LFA-1 involved in transendothelial migration of leukocytes

Nature Immunology volume 3, pages 151–158 (2002)Cite this article

Abstract

Inflammatory recruitment of leukocytes is governed by dynamic interactions between integrins and endothelial immunoglobulin superfamily (IgSF) proteins. We have identified the IgSF member junctional adhesion molecule 1 (JAM-1) as a ligand of the β2 integrin lymphocyte function–associated antigen 1 (LFA-1). Under static and physiological flow conditions, JAM-1 contributed to LFA-1–dependent transendothelial migration of T cells and neutrophils as well as LFA-1–mediated arrest of T cells. The latter was triggered by chemokines on endothelium that was stimulated with cytokines to redistribute JAM-1 from the tight junctions. Transfectants expressing JAM-1 supported LFA-1–mediated adhesion of leukocytes, which required the membrane-proximal Ig-like domain 2 of JAM-1. Thus, JAM-1 is a counter-receptor for LFA-1 that is ideally situated to guide and control transmigration during leukocyte recruitment.

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Figure 1: Expression of JAM-1.
Figure 2: JAM-1 serves as ligand for LFA-1–bearing Jurkat T cells and purified LFA-1.
Figure 3: Interaction with JAM-1 is specific for the β2 integrin LFA-1 but not Mac-1.
Figure 4: Expression of JAM-1 domain deletion mutants in CHO cells.
Figure 5: The membrane-proximal domain 2 of JAM-1 mediates interactions with LFA-1.
Figure 6: JAM-1 participates in LFA-1–dependent adhesion and transmigration of T cells on endothelium triggered by PMA or SDF-1α under static or physiological flow conditions.
Figure 7: JAM-1 contributes to LFA-1–mediated transmigration but not arrest of neutrophils.

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Acknowledgements

We thank P. C. Weber for continuous support, G. Heiss for initial support and advice and N. Gellert for expert technical assistance. Supported by Deutsche Forschungsgemeinschaft (grant WE-1913/2 to C. W.).

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  1. Institute for Prevention of Cardiovascular Diseases, Ludwig-Maximilians-University, Munich, Germany

    Georg Ostermann, Kim S. C. Weber, Alma Zernecke, Andreas Schröder & Christian Weber

  2. Department of Molecular Cardiovascular Research, University Hospital Aachen, Rheinisch-Westfälische Technische Hochschule, Pauwelsstrasse 30, Aachen, 52074, Germany

    Georg Ostermann & Christian Weber

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Ostermann, G., Weber, K., Zernecke, A. et al. JAM-1 is a ligand of the β2 integrin LFA-1 involved in transendothelial migration of leukocytes. Nat Immunol 3, 151–158 (2002). https://doi.org/10.1038/ni755

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