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1 Department of Genomics and Pathobiology, University of Alabama at Birmingham, Birmingham, AL, USA
2 Department of Pathology, Louisiana State University Health Sciences Center, Birmingham, AL, USA
3 Research Service, University of Alabama at Birmingham, Birmingham VA Medical Center, Birmingham, AL, USA
* To whom correspondence should be addressed. E-mail: kucik{at}uab.edu.
Leukocyte rolling, adhesion, and migration on vascular endothelium involve several sets of adhesion molecules that interact simultaneously. Each of these receptor-ligand pairs may play multiple roles. We examined the role of ICAM-1 in adhesive interactions using mouse aortic endothelial cells (MAECs) in an in vitro flow system. Average rolling velocity of the monocytic cell line WEHI 274.1 was increased on ICAM-1 deficient MAECs compared to wild type, both with and without TNF-
stimulation. High-temporal-resolution analysis provided insights into the underlying basis for these differences. Without TNF- stimulation, average rolling velocity was slower on wild type than ICAM-1 deficient endothelium due to brief (< 1 second) pauses. On TNF- stimulated ICAM-1 deficient endothelium, cells rolled faster due to transient accelerations, producing "jerky" rolling. Firm adhesion to ICAM-1 deficient MAEC was significantly reduced compared to wild type, although the number of rolling cells was similar. These results demonstrate directly that ICAM-1 affects rolling velocity by stabilizing leukocyte rolling.
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