Abstract
The signaling events leading to the activation of integrins and firm arrest of rolling neutrophils in inflamed venules have yet to be elucidated. In vitro assays suggest that both E-selectin and chemokines can trigger arrest of rolling neutrophils, but E-selectin-/- mice have normal levels of adherent neutrophils in inflamed venules. To test whether chemokine-induced neutrophil arrest in vivo can be unmasked by blocking E-selectin, we investigated neutrophil adhesion in inflamed cremaster muscle venules in tumor necrosis factor (TNF)-α-treated CXCR2-/- or wild-type (WT) mice injected with E-selectin blocking monoclonal antibody (mAb) 9A9. To block chemokine receptor signaling, we investigated E-selectin-/- or WT mice treated with pertussis toxin (PTx) intravenously. Neutrophil adhesion was unchanged in CXCR2-/-, E-selectin-/-, PTx-treated WT, or mAb 9A9-treated WT mice. However, TNF-α-induced neutrophil adhesion was almost completely abrogated in E-selectin-/- mice treated with PTx and significantly reduced in CXCR2-/- mice treated with the E-selectin blocking mAb. In thioglycollate-induced peritonitis, PTx treatment blocked neutrophil recruitment into the peritoneum of E-selectin-/- mice, but had only a partial effect in WT animals. These data show that E-selectin- and chemokine-mediated arrest mechanisms are overlapping in this model and identify CXCR2 as an important neutrophil arrest chemokine in vivo.
Original language | English (US) |
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Pages (from-to) | 935-939 |
Number of pages | 5 |
Journal | Journal of Experimental Medicine |
Volume | 200 |
Issue number | 7 |
DOIs | |
State | Published - Oct 4 2004 |
Externally published | Yes |
Keywords
- Chemokine
- E-selectin
- G protein-coupled receptors
- Neutrophils
- Pertussis toxin
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology