Allergic airway disease is unaffected by the absence of IL-4R[alpha]-dependent alternatively activated macrophages

• Published in: Journal of allergy and clinical immunology Vol. 130; no. 3; pp. 743 - 750.e8
• Main Authors: Nieuwenhuizen, Natalie E, Kirstein, Frank, Jayakumar, Jaisubash, Emedi, Babele, Hurdayal, Ramona, Horsnell, William GC, Lopata, Andreas L, Brombacher, Frank
• Format: Journal Article
• Language: English
• Published: St. Louis Elsevier Limited 01.09.2012
• Subjects: Cloning; Colleges & universities; Disease; Flow cytometry; Lungs; Polyamines; Respiratory diseases; South Africa
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.03.011

Background Markers of alternatively activated macrophages (AAMs) are upregulated in the lungs of asthmatic patients and in mice with allergic airway disease. AAMs are thought to contribute to the pathogenesis of allergic airway disease by virtue of their decreased NO production and increased production of proline and polyamines, which are important in the synthesis of connective tissues such as collagen. Objective We aimed to define the role of AAMs in the pathogenesis of allergic airway disease. Methods The IL-4 receptor alpha (IL-4Rα) gene is genetically abrogated in macrophages in LysMcreIL-4Rα-/loxmice, which therefore have impaired IL-4/IL-13 activation of AAMs through IL-4R types 1 and 2. Responses of LysMcreIL-4Rα-/loxmice and IL-4Rα-/loxlittermate controls were examined in ovalbumin- and house dust mite-induced allergic airway disease. Results IL-4Rα expression was shown to be efficiently depleted from alveolar macrophages, interstitial macrophages, and CD11b+MHCII+inflammatory macrophages. Although the expression of markers of AAMs such as Ym-1, arginase and found in inflammatory zone 1 was decreased in macrophages of LysMcreIL-4Rα-/loxmice in chronic ovalbumin-induced allergic airway disease, airway hyperreactivity, TH2 responses, mucus hypersecretion, eosinophil infiltration, and collagen deposition were not significantly reduced. LysMcreIL-4Rα-/loxmice and littermate controls also developed similar responses in acute ovalbumin- and house dust mite-induced allergic airway disease. Conclusion Our results suggest that the presence of AAMs in allergic airway disease may be only an association, as a result of the increased TH2 responses present during disease, and that IL-4Rα-dependent AAMs do not play an important role in the pathology of disease.