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

U Jung, KE Norman… - The Journal of …, 1998 - Am Soc Clin Investig
U Jung, KE Norman, K Scharffetter-Kochanek, AL Beaudet, K Ley
The Journal of clinical investigation, 1998Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation