PMID- 9710121 OWN - NLM STAT- MEDLINE DCOM- 19980901 LR - 20190706 IS - 0009-7330 (Print) IS - 0009-7330 (Linking) VI - 83 IP - 3 DP - 1998 Aug 10 TI - Importance of E-selectin for firm leukocyte adhesion in vivo. PG - 287-94 AB - 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. FAU - Ley, K AU - Ley K AD - Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908, USA. kf13f@virginia.edu FAU - Allietta, M AU - Allietta M FAU - Bullard, D C AU - Bullard DC FAU - Morgan, S AU - Morgan S LA - eng GR - R01 AI-32177/AI/NIAID NIH HHS/United States GR - R01 HL-54136/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Circ Res JT - Circulation research JID - 0047103 RN - 0 (Chemokine CXCL2) RN - 0 (Chemotactic Factors) RN - 0 (E-Selectin) RN - 0 (Monokines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) SB - IM MH - Animals MH - Cell Adhesion/drug effects MH - Cell Movement/drug effects MH - Chemokine CXCL2 MH - Chemotactic Factors/administration & dosage/pharmacology MH - E-Selectin/*physiology MH - Hemodynamics/drug effects MH - Intercellular Adhesion Molecule-1/physiology MH - Leukocyte Count MH - Leukocytes/drug effects/*physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microinjections MH - Monokines/administration & dosage/pharmacology MH - N-Formylmethionine Leucyl-Phenylalanine/administration & dosage/pharmacology MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 1998/08/26 00:00 MHDA- 1998/08/26 00:01 CRDT- 1998/08/26 00:00 PHST- 1998/08/26 00:00 [pubmed] PHST- 1998/08/26 00:01 [medline] PHST- 1998/08/26 00:00 [entrez] AID - 10.1161/01.res.83.3.287 [doi] PST - ppublish SO - Circ Res. 1998 Aug 10;83(3):287-94. doi: 10.1161/01.res.83.3.287.