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

J Clin Invest. 1998 Oct 15;102(8):1526-33. doi: 10.1172/JCI119893.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD18 Antigens / genetics
  • CD18 Antigens / metabolism*
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Chemotaxis, Leukocyte / physiology*
  • Cytokines / pharmacology*
  • E-Selectin / metabolism*
  • Hemodynamics
  • Inflammation / etiology
  • Leukocyte Count
  • Mice
  • Mice, Mutant Strains
  • Models, Biological
  • Time Factors
  • Venules / physiology*


  • CD18 Antigens
  • Cytokines
  • E-Selectin