Differential roles for endothelial ICAM-1, ICAM-2, and VCAM-1 in shear-resistant T cell arrest, polarization, and directed crawling on blood-brain barrier endothelium.
Endothelial ICAM-1 and ICAM-2 were shown to be essential for T cell diapedesis across the blood-brain barrier (BBB) in vitro under static conditions. Crawling of T cells prior to diapedesis was only recently revealed to occur preferentially against the direction of blood flow on the endothelial surface of inflamed brain microvessels in vivo. Using live cell-imaging techniques, we prove that Th1 memory/effector T cells predominantly crawl against the direction of flow on the surface of BBB endothelium in vitro. Analysis of T cell interaction with wild-type, ICAM-1-deficient, ICAM-2-deficient, or ICAM-1 and ICAM-2 double-deficient primary mouse brain microvascular endothelial cells under physiological flow conditions allowed us to dissect the individual contributions of endothelial ICAM-1, ICAM-2, and VCAM-1 to shear-resistant T cell arrest, polarization, and crawling. Although T cell arrest was mediated by endothelial ICAM-1 and VCAM-1, T cell polarization and crawling were mediated by endothelial ICAM-1 and ICAM-2 but not by endothelial VCAM-1. Therefore, our data delineate a sequential involvement of endothelial ICAM-1 and VCAM-1 in mediating shear-resistant T cell arrest, followed by endothelial ICAM-1 and ICAM-2 in mediating T cell crawling to sites permissive for diapedesis across BBB endothelium.
Steiner
Oliver
O
Theodor Kocher Institute, University of Bern, Bern, Switzerland.
Coisne
Caroline
C
Cecchelli
Roméo
R
Boscacci
Rémy
R
Deutsch
Urban
U
Engelhardt
Britta
B
Lyck
Ruth
R
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C480027:ICAM-2 protein, mouse; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1