title: Phenotypic plasticity and targeting of Siglec-F(high) CD11c(low) eosinophils to the airway in a murine model of asthma.
abstract: Eosinophil recruitment in asthma is a multistep process, involving both trans-endothelial migration to the lung interstitium and trans-epithelial migration into the airways. While the trans-endothelial step is well studied, trans-epithelial recruitment is less understood. To contrast eosinophil recruitment between these two compartments, we employed a murine kinetics model of asthma. Eosinophils were phenotyped by multicolor flow cytometry in digested lung tissue and bronchoalveolar lavage (BAL) simultaneously, 6 h after each ovalbumin (OVA) challenge. There was an early expansion of tissue eosinophils after OVA challenge followed by eosinophil buildup in both compartments and a shift in phenotype over the course of the asthma model. Gradual transition from a Siglec-F(med) CD11c(-) to a Siglec-F(high) CD11c(low) phenotype in lung tissue was associated with eosinophil recruitment to the airways, as all BAL eosinophils were of the latter phenotype. Secondary microarray analysis of tissue-activated eosinophils demonstrated upregulation of specific integrin and chemokine receptor signature suggesting interaction with the mucosa. Using adhesion assays, we demonstrated that integrin CD11c mediated adhesion of eosinophils to fibrinogen, a significant component of epithelial barrier repair and remodeling. To the best of our knowledge, this is the only report to date dissecting compartmentalization of eosinophil recruitment as it unfolds during allergic inflammation. By capturing the kinetics of eosinophil phenotypic change in both tissue and BAL using flow cytometry and sorting, we were able to demonstrate a previously undocumented association between phenotypic shift of tissue-recruited eosinophils and their trans-epithelial movement, which implicates the existence of a specific mechanism targeting these cells to mucosal airways.
authors.affiliation: Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: H
authors.initials: H
authors.lastname: Abdala Valencia
authors.affiliation: Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Loffredo
authors.affiliation: Division of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Misharin
authors.affiliation: Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Berdnikovs
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism*; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D016130:Immunophenotyping; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010641:Phenotype
chemical_list: D039521:CD11c Antigen
keywords: allergic inflammation; eosinophils; integrins; phenotypic plasticity; recruitment kinetics