title: Contribution of endothelial selectins and alpha 4 integrins to eosinophil trafficking in allergic and nonallergic inflammatory reactions in skin.
abstract: The role of endothelial selectins in mediating eosinophil recruitment was assessed using the trafficking of 111In-labeled blood eosinophils in mouse skin. An intradermal injection of chemoattractants (leukotriene B4, macrophage inflammatory protein-l alpha, and eotaxin) resulted in a rapid accumulation of 111In eosinophils that was reduced 49 to 91% by anti-P-selectin mAb. An anti-E-selectin mAb was ineffective, although a combined E- and P-selectin blockade resulted in >95% inhibition of all responses. The accumulation of a pulse of 111In eosinophils at sites of active cutaneous anaphylaxis (ACA) at 4 to 8 h and at 20 to 24 h after Ag challenge was completely dependent upon E- and P-selectin in combination, but not in isolation. In contrast, at 20 to 24 h after Ag challenge in a delayed-type hypersensitivity (DTH) reaction in skin, 111In eosinophil accumulation was largely independent of endothelial selectins, even when L-selectin was also blocked. An anti-alpha 4 integrin mAb significantly reduced 111In eosinophil trafficking in both allergic reactions but was slightly more effective in the DTH reaction compared with the ACA reaction. These results show that P-selectin and to a lesser extent E-selectin mediate eosinophil recruitment in skin in acute inflammatory reactions. In allergic, late-onset inflammatory reactions, neither P- nor E-selectin alone are sufficient to mediate eosinophil accumulation; when combined, they are essential for trafficking in ACA but are less important in the DTH reaction. Whether alpha 4 integrin-based strategies will be more effective than selectin-based strategies at inhibiting eosinophil recruitment in human disease remains to be determined.
authors.affiliation: Applied Pharmacology, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom.
authors.forename: M M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: P G
authors.initials: PG
authors.lastname: Hellewell
mesh_terms: D000707:Anaphylaxis / Q000276:immunology / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology; D002465:Cell Movement / Q000276:immunology*; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D039441:Integrin alpha4; D051379:Mice; D008808:Mice, Inbred CBA; D019007:P-Selectin / Q000096:biosynthesis / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D002631:Chemotactic Factors, Eosinophil; D019040:E-Selectin; D019007:P-Selectin; D039441:Integrin alpha4