Importance of E-selectin for firm leukocyte adhesion in vivo.
Leukocyte adhesion under flow is preferentially mediated by the selectins. In this study we used intravital microscopy to investigate whether E-selectin may promote firm leukocyte adhesion in vivo. E-Selectin is expressed by endothelial cells activated with tumor necrosis factor-alpha (TNF-alpha) and causes slow leukocyte rolling. Microinjection of formyl-methionyl-leucyl-phenylalanine (fMLP) or macrophage inflammatory protein-2 (MIP-2) next to a venule of the TNF-alpha-treated mouse cremaster muscle significantly increased the number of adherent leukocytes. In gene-targeted mice homozygous for a null mutation in the E-selectin gene or in wild-type mice treated with an E-selectin monoclonal antibody (mAb), this response was significantly attenuated (by >80%). No such defect was seen in intercellular adhesion molecule-1 (ICAM-1)-deficient mice. E-Selectin-null mice showed more rapid leukocyte rolling than wild-type or ICAM-1-deficient mice, resulting in significantly shortened leukocyte transit times through venules. Topical application of fMLP onto the whole cremaster muscle generated the same number of adherent leukocytes in wild-type and E-selectin-deficient mice. We conclude that slow leukocyte rolling through E-selectin results in long transit times, which are essential for efficient leukocyte adhesion in response to a local chemotactic stimulus.
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908, USA. kf13f@virginia.edu
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D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000008:administration & dosage / Q000494:pharmacology; D019040:E-Selectin / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D015846:Monokines / Q000008:administration & dosage / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D019040:E-Selectin; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009240:N-Formylmethionine Leucyl-Phenylalanine