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Published in Volume 102, Issue 8 (October 15,1998)
J. Clin. Invest. 102(8): 1526-1533 (1998). doi:10.1172/JCI119893.
Copyright © 1998, The American Society for Clinical Investigation.

Research Article

Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo.

U Jung, K E Norman, K Scharffetter-Kochanek, A L Beaudet and K Ley

Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.

Published October 15, 1998

Leukocyte recruitment requires leukocyte rolling, activation, firm adhesion, and transmigration. Injection of the proinflammatory cytokine TNF-alpha induces expression of E-selectin, interleukin-8, and other adhesion molecules and chemoattractants on the endothelial surface. TNF-alpha- treated CD18 null mouse cremaster muscle venules show increased leukocyte rolling velocity and reduced leukocyte recruitment efficiency. Leukocyte recruitment in CD18 null but not wild-type mice is significantly blocked by an mAb to E-selectin. To understand this overlap between adhesion events previously considered separate, we introduce a quantitative analysis of the efficiency of induction of rolling, conversion of rolling to adhesion, and of adhesion to transmigration. We find that CD18 and E-selectin cooperate to control the time a leukocyte needs to roll through an inflamed area and to convert rolling to firm adhesion. Leukocyte rolling time, defined as the time it takes for a rolling leukocyte to pass through a defined length of a vessel segment, emerges as a unifying parameter determining the efficiency of inducing firm adhesion, which is a rate-limiting step controlling leukocyte recruitment in inflammation. We conclude that leukocytes integrate chemoattractant signals while rolling along the endothelial surface until they reach a critical level of activation and become firmly adherent.

This article Copyright © 1998, The American Society for Clinical Investigation.

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