title: Allergic airway disease is unaffected by the absence of IL-4Rα-dependent alternatively activated macrophages.
abstract: 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 LysM(cre)IL-4Rα(-/lox) mice, which therefore have impaired IL-4/IL-13 activation of AAMs through IL-4R types 1 and 2. Responses of LysM(cre)IL-4Rα(-/lox) mice and IL-4Rα(-/lox) littermate 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 LysM(cre)IL-4Rα(-/lox) mice in chronic ovalbumin-induced allergic airway disease, airway hyperreactivity, T(H)2 responses, mucus hypersecretion, eosinophil infiltration, and collagen deposition were not significantly reduced. LysM(cre)IL-4Rα(-/lox) mice and littermate controls also developed similar responses in acute ovalbumin- and house dust mite-induced allergic airway disease.
  
  
  CONCLUSIONS
  Our results suggest that the presence of AAMs in allergic airway disease may be only an association, as a result of the increased T(H)2 responses present during disease, and that IL-4Rα-dependent AAMs do not play an important role in the pathology of disease.
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Cape Town, South Africa.
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Nieuwenhuizen
authors.forename: Frank
authors.initials: F
authors.lastname: Kirstein
authors.forename: Jaisubash
authors.initials: J
authors.lastname: Jayakumar
authors.forename: Babele
authors.initials: B
authors.lastname: Emedi
authors.forename: Ramona
authors.initials: R
authors.lastname: Hurdayal
authors.forename: William G C
authors.initials: WG
authors.lastname: Horsnell
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Lopata
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000403:Airway Resistance; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology*; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000502:physiology*; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D003094:Collagen; D016207:Cytokines; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit