title: Attenuation of airway hyperresponsiveness in a murine asthma model by neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF).
abstract: Asthma is recognized as an inflammatory disease in which various cytokines are involved. Among these, granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to play a critical role in the survival of eosinophils and in the activation of antigen-presenting cells (APC). We studied the effects of neutralization of GM-CSF in a murine model of asthma, to elucidate its role in enhanced airway responsiveness and in airway inflammation. A/J mice, which are genetically predisposed to acetylcholine hyperresponsiveness, were immunized with ovalbumin (OA) and alum. Thereafter, the mice were subjected to a two-week regimen of OA inhalation, during which either goat anti-mouse polyclonal GM-CSF antibody or isotype control goat IgG was administered intranasally. Pulmonary function was then analyzed using whole body plethysmography before and after acetylcholine (Ach) inhalation. Here we show that OA inhalation following OA immunization increased airway responsiveness to acetylcholine and induced GM-CSF as well as IL-4 and IL-5 mRNA expression in the lung. The administration of GM-CSF-neutralizing antibody during OA inhalation significantly reduced this increased airway hyperresponsiveness and also inhibited airway inflammation. Thus, endogenous GM-CSF plays an important role in the process of airway inflammation and airway hyperresponsiveness after antigen-specific immunity has been established.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Yamashita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tashimo
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Ishida
authors.forename: Fujito
authors.initials: F
authors.lastname: Kaneko
authors.forename: Junichi
authors.initials: J
authors.lastname: Nakano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kato
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirai
authors.forename: Tadashi
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000276:immunology*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D010047:Ovalbumin; D010991:Plethysmography
chemical_list: D019138:Antibodies, Blocking; D007074:Immunoglobulin G; D015848:Interleukin-5; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin