A role for ICAM-1 in maintenance of leukocyte-endothelial cell rolling interactions in inflamed arterioles

• Published in: American journal of physiology. Heart and circulatory physiology 2007-11, Vol.293 (5), p.H2786-H2798
• Main Authors: Sumagin, Ronen, Sarelius, Ingrid H
• Format: Article
• Language: English
• Subjects: Animals; Arterioles - drug effects; Arterioles - immunology; Arterioles - pathology; Cell adhesion & migration; Cell Communication - drug effects; Cell Communication - immunology; Cell Movement - drug effects; Cell Movement - immunology; Cells; Cells, Cultured; Endothelial Cells - drug effects; Endothelial Cells - immunology; Gene expression; Intercellular Adhesion Molecule-1 - immunology; Leukocytes; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Male; Mice; Mice, Knockout; Proteins; Rodents; Studies; Tumor Necrosis Factor-alpha; Vasculitis - chemically induced; Vasculitis - immunology; Vasculitis - pathology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00720.2007

1 Department of Biomedical Engineering and 2 Department of Pharmacology and Physiology, University of Rochester, Rochester, New York Submitted 20 June 2007 ; accepted in final form 13 August 2007 A key endothelial receptor in leukocyte-endothelial cell (EC) interactions is ICAM-1. ICAM-1 is constitutively expressed at low levels on vascular ECs, and its levels significantly increase following stimulation with many proinflammatory agents. This study provides evidence that in inflamed arterioles of anesthetized mice (65 mg/kg ip Nembutal), ICAM-1 mediates leukocyte rolling, in contrast to its expected role of mediating firm adhesion in venules. The number of leukocytes rolling on arteriolar ECs is decreased in ICAM-1 knockout (KO) compared with wild-type (WT) mice (KO, 6.0 ± 0.9; WT, 12.0 ± 1.0 leukocytes/40 s; P < 0.05), whereas the leukocyte-rolling number in venules remains unaffected (KO, 5.6 ± 0.9; WT, 7.0 ± 0.7 leukocytes/40 s; n = 13–15 sites). We also show that the fraction of leukocytes that is rolling on arteriolar ECs does so with a higher characteristic velocity (>70 µm/s), and, furthermore, that the distance over which rolling contacts with the arteriolar wall are maintained is ICAM-1 dependent. In ICAM-1 KO animals or in WT mice in the presence of ICAM-1-blocking antibody, leukocytes rolled significantly shorter distances over the sampled 200-µm vessel length compared with WT (68 ± 6.7 and 55 ± 9.4 vs. 85 ± 12.9% total, respectively, n = 4 sites, P < 0.05). We also found evidence that in ICAM-1 KO mice, a significant fraction of leukocyte rolling and adhesive interactions with arteriolar ECs could be accounted for by upregulation of another adhesion molecule, VCAM-1, providing an important illustration of how expression of related proteins can be altered following genetic ablatement of a target molecule (in this case ICAM-1). intracellular adhesion molecule-1 knockout mice; intracellular adhesion molecule-1; vascular cell adhesion molecule-1; leukocyte adhesion; leukocyte rolling; tumor necrosis factor- ; in vivo; intravital confocal microscopy Address for reprint requests and other correspondence: I. H. Sarelius, Dept. of Pharmacology and Physiology, Univ. of Rochester, Medical Center, Box 711, Rochester, NY 14642 (e-mail: ingrid_sarelius{at}urmc.rochester.edu )