Abstract
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-α (TNF- α) 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-α-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-l-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.
Original language | English (US) |
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Pages (from-to) | 287-294 |
Number of pages | 8 |
Journal | Circulation research |
Volume | 83 |
Issue number | 3 |
DOIs | |
State | Published - Aug 10 1998 |
Externally published | Yes |
Keywords
- E-selectin
- ICAM-1
- Leukocyte adhesion
- Leukocyte transit
- Rolling
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine