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

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 mu m/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-mu m 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).