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J. Exp. Med.,
Volume 189, Number 9, May 3, 1999 1467-1478
By
¶
From the * Leukocyte Adhesion Laboratory and the Using lymphocyte function-associated antigen (LFA)-1 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
/ 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
4 integrins, 4
7 and 41, 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 4 monoclonal antibodies. Unexpectedly, vascular cell adhesion molecule (VCAM)-1,
which is essential in inflammatory responses, serves as the ligand for the 4 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
47-specific ligand, dominates. Both 41, 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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