Overlapping and selective roles of endothelial intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 in lymphocyte trafficking.
The integrin LFA-1 interacts with a variety of ligands termed ICAMs. ICAM-1 and ICAM-2 are both expressed on endothelium and serve as counterreceptors during lymphocyte trafficking. In this study, we analyzed their relative contribution to lymphocyte recirculation through lymph nodes and to recruitment into lung and inflamed skin by blocking mAbs against ICAM-1 and ICAM-2 and mice deficient for ICAM-1. The entry of lymphocytes into peripheral and mesenteric lymph nodes was found to be unaffected by the functional deletion of either ICAM-1 or ICAM-2. However, when both pathways were blocked, recirculation through lymph nodes was strongly reduced. Trapping of lymphocytes in the lung after i.v. injection is partly mediated by LFA-1/ICAM interactions; the data presented in this study show an exclusive role of ICAM-1 in LFA-1-dependent lung trapping. Similarly, ICAM-1, but not ICAM-2, was required for the migration of T effector cells into the inflamed skin. These results indicate that ICAM-1 and ICAM-2 have redundant functions in lymphocyte recirculation through lymph nodes, but ICAM-1 is unique in supporting migration into inflamed sites and trapping within the lung.
Lehmann
Joachim C U
JC
Experimentelle Rheumatologie, Universitätsklinik Charité, Humboldt-Universität and Deutsches Rheumaforschungszentrum, Schumannstrasse 21/22, 10117 Berlin, Germany.
Jablonski-Westrich
Dorothee
D
Haubold
Uta
U
Gutierrez-Ramos
Jose-C
JC
Springer
Timothy
T
Hamann
Alf
A
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000502:physiology*; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology / Q000502:physiology; D016131:Lymphocyte Subsets / Q000473:pathology / Q000502:physiology*; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010581:Peyer's Patches / Q000166:cytology / Q000502:physiology; D012867:Skin / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D018799:Intercellular Adhesion Molecule-1