Prolonged Eosinophil Production after Allergen Exposure in IFN-γR KO Mice is IL-5 Dependent.

Autor: Zhao, L.-L., Lötvall, J., Lindén, A., Tomaki, M., Sjöstrand, M., Bossios, A.
Předmět:
Zdroj: Scandinavian Journal of Immunology; May2008, Vol. 67 Issue 5, p480-488, 9p, 1 Color Photograph, 1 Diagram, 1 Chart, 3 Graphs
Abstrakt: Asthma is a T helper 2 (Th2)-driven inflammatory process characterized by eosinophilia. Prolonged airway eosinophilia is commonly observed in asthma exacerbations. Our aim was to evaluate whether eosinophilia in prolonged allergic inflammation is associated with a continuous supply of new eosinophils to the airways, and how this is regulated. Ovalbumin (OVA)-sensitized interferon-γ receptor knockout mice (IFN-γR KO), known to maintain a long-lasting eosinophilia after allergen exposure, were compared to wild type (wt) controls. Animals were exposed to OVA or phosphate-buffered saline on three consecutive days, and bone marrow (BM), blood and bronchoalveolar lavage (BAL) samples were collected 24 h, 7 and 21 days later. Newly produced cells were labelled using bromodeoxyuridine (BrdU). Serum IL-5 was measured and its role was investigated by administration of a neutralizing anti-IL-5 antibody. In-vitro eosinophilopoiesis was examined in both groups by a colony-forming assay. Allergen challenge increased eosinophils in BM, blood and BAL, in both IFN-γR KO and wt mice, both 24 h and 7 days after the last allergen exposure. At 21 days after the last exposure, only IFN-γR KO mice maintained significantly increased eosinophil numbers. Approximately 50% of BAL granulocytes in IFN-γR KO were produced during the last 6 days. Interleukin (IL)-5 concentration was increased in IFN-γR KO mice, and anti-IL-5 reduced eosinophil numbers in all compartments. Increased numbers of eosinophil colonies were observed in IFN-γR KO mice after allergen exposure versus controls. In this model of a Th2-driven prolonged allergic eosinophilia, new eosinophils contribute to the extended inflammation in the airways by enhanced BM eosinophilopoiesis in an IL-5-dependent manner. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index