title: Granulocyte-macrophage colony-stimulating factor and lung immunity in pulmonary alveolar proteinosis.
abstract: The anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody is inferred to cause idiopathic pulmonary alveolar proteinosis (iPAP): the antibody neutralizes GM-CSF and thereby impairs differentiation of alveolar macrophages. Administration of GM-CSF improves respiratory function of patients with iPAP, as confirmed in this study using aerosolized GM-CSF. To elucidate its mechanism, we characterized bronchoalveolar lavage fluid and alveolar macrophages obtained from three patients with iPAP who were treated successfully with aerosolized GM-CSF. Cell number, expressions of surface mannose receptor and the transcription factor PU.1, and phagocytic ability of alveolar macrophages were all restored to control levels. With treatment, the neutralizing capacity of GM-CSF activity was reduced markedly, concomitant with the decreasing autoantibody levels. Interestingly, the amount of GM-CSF autoantibody complex also decreased. In one case in which the complex was analyzed, the majority of GM-CSF binding the complex was endogenous protein, suggesting that the complex is removed immediately from the lung after treatment. Our study shows that GM-CSF administration engenders a decrease in the neutralizing capacity against the protein in the lungs. Thereby, it facilitates restoration of the normal function of alveolar macrophages.
authors.affiliation: Institute of Development, Aging, and Cancer, Tohoku University; Department of Hematology and Immunology, Tohoku University Hospital, Japan.
authors.forename: Ryushi
authors.initials: R
authors.lastname: Tazawa
authors.forename: Emi
authors.initials: E
authors.lastname: Hamano
authors.forename: Toru
authors.initials: T
authors.lastname: Arai
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Ohta
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishimoto
authors.forename: Kanji
authors.initials: K
authors.lastname: Uchida
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.forename: Junichi
authors.initials: J
authors.lastname: Saito
authors.forename: Miki
authors.initials: M
authors.lastname: Takeshita
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ishige
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Masahito
authors.initials: M
authors.lastname: Ebina
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D001323:Autoantibodies / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011649:Pulmonary Alveolar Proteinosis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000336:Aerosols; D001323:Autoantibodies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor