Using lymphocyte function-associated antigen (LFA)-1−/− mice, we have examined the role of LFA-1 and other integrins in the recirculation of lymphocytes. LFA-1 has a key role in migration to peripheral lymph nodes (pLNs), and influences migration into other LNs. Second, the α4 integrins, α4β7 and α4β1, have a hitherto unrecognized ability to compensate for the lack of LFA-1 in migration to pLNs. These findings are confirmed using normal mice and blocking LFA-1 and α4 monoclonal antibodies. Unexpectedly, vascular cell adhesion molecule (VCAM)-1, which is essential in inflammatory responses, serves as the ligand for the α4 integrins on pLN high endothelial venules. VCAM-1 also participates in trafficking into mesenteric LNs and Peyer's patch nodes where mucosal addressin cell adhesion molecule 1 (MAdCAM-1), the α4β7-specific ligand, dominates. Both α4β1, interacting with ligand VCAM-1, and also LFA-1 participate in substantial lymphocyte recirculation through bone marrow. These observations suggest that organ-specific adhesion receptor usage in mature lymphocyte recirculation is not as rigidly adhered to as previously considered, and that the same basic sets of adhesion receptors are used in both lymphocyte homing and inflammatory responses.
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3 May 1999
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May 03 1999
Lymphocyte Migration in Lymphocyte Function-associated Antigen (LFA)-1–deficient Mice
Cornelia Berlin-Rufenach,
Cornelia Berlin-Rufenach
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
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Florian Otto,
Florian Otto
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
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Meg Mathies,
Meg Mathies
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
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Juergen Westermann,
Juergen Westermann
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
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Michael J. Owen,
Michael J. Owen
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
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Alf Hamann,
Alf Hamann
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
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Nancy Hogg
Nancy Hogg
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
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Cornelia Berlin-Rufenach
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
Florian Otto
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
Meg Mathies
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
Juergen Westermann
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
Michael J. Owen
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
Alf Hamann
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
Nancy Hogg
From the *Leukocyte Adhesion Laboratory and the ‡Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; the §Center of Anatomy, Medical School of Hannover, D-30623 Hannover, Germany; the ‖Department of Immunology, Medical Clinic, University Hospital Eppendorf, D-20246 Hamburg, Germany; and ¶Charité Clinic, Humboldt University, D-10117 Berlin, Germany
Address correspondence to Nancy Hogg, Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, UK. Phone: 44-171-269-3255; Fax: 44-171-269-3093; E-mail: [email protected]
C. Berlin-Rufenach was supported by an EMBO Fellowship. F. Otto was supported by Deutsche Forschungsgemeinschaft fellowship Ot 134/1-1. M. Mathies was supported by The Claremont Colleges, Claremont, CA. This work was funded by the Deutsche Forschungsgemeinschaft (A. Hamann) and the Imperial Cancer Research Fund.
F. Otto's present address is University of Freiburg Medical Center, 79106 Freiburg, Germany, and M. Mathies's is Joint Science Department, Claremont Colleges, Claremont, CA 91711.
C. Berlin-Rufenach, F. Otto, and M. Mathies contributed equally to this manuscript.
Received:
September 17 1998
Revision Received:
February 25 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (9): 1467–1478.
Article history
Received:
September 17 1998
Revision Received:
February 25 1999
Citation
Cornelia Berlin-Rufenach, Florian Otto, Meg Mathies, Juergen Westermann, Michael J. Owen, Alf Hamann, Nancy Hogg; Lymphocyte Migration in Lymphocyte Function-associated Antigen (LFA)-1–deficient Mice . J Exp Med 3 May 1999; 189 (9): 1467–1478. doi: https://doi.org/10.1084/jem.189.9.1467
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