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    IL-4 activates equine neutrophils and induces a mixed inflammatory cytokine expression profile with enhanced neutrophil chemotactic mediator release ex vivo (2010)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Lavoie-Lamoureux, Anouk
    Moran, Kantuta
    Beauchamp, Guy
    Mauel, Susanne
    Steinbach, Falko
    Lefebvre-Lavoie, Josiane
    Martin, James G
    Lavoie, Jean-Pierre
    Quelle
    American journal of physiology / Lung cellular and molecular physiology; 299(4) — S. L472–L482
    ISSN: 1522-1504
    Sprache
    Englisch
    Verweise
    DOI: 10.1152/ajplung.00135.2009
    Pubmed: 20639353
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    Tel.+49 30 838 62450 Fax.+49 30 838 62522

    Abstract / Zusammenfassung

    Neutrophils are potent contributors to the lung pathophysiological changes occurring in allergic airway inflammation, which typically involve T helper type 2 (Th2) cytokine overexpression. We have previously reported that equine pulmonary endothelial cells are activated by the Th2 cytokine IL-4 and express chemotactic factors for neutrophils after stimulation. We have further explored the possible mechanisms linking Th2-driven inflammation and neutrophilia by studying the effects of recombinant equine IL-4, a prototypical Th2 cytokine, on peripheral blood neutrophils (PBN) isolated from normal animals and from horses with asthmatic airway inflammation (equine heaves). We found that IL-4 induced morphological changes in PBN, dose- and time-dependent expression of IL-8 mRNA, as well as the release of chemotactic factors for neutrophils in culture supernatants. Also, IL-4 induced a mixed inflammatory response in PBN from control and asthmatic-animals with increased expression of proinflammatory IL-8 and TNF-α but a marked inhibition of IL-1β. IL-4 type I receptor (IL-4Rα) and CD23 (FcεRII) expression were also upregulated by IL-4. Importantly, disease as well as chronic antigenic exposure modified gene expression by PBN. Finally, we found that activation of equine neutrophils with IL-4 involved STAT6 phosphorylation and p38 MAPK and phosphatidylinositol 3-kinase (PI3K); the pharmacological inhibitors, SB-203580 and LY-294002, respectively, significantly reversed IL-4-induced gene modulation in PBN. Overall, results from this study add to the link between Th2-driven inflammation and neutrophilia in the equine model and further extend the characterization of IL-4 effects on neutrophils.