title: Surfactant protein D regulates airway function and allergic inflammation through modulation of macrophage function.
abstract: The lung collectin surfactant protein D (SP-D) is an important component of the innate immune response but is also believed to play a role in other regulatory aspects of immune and inflammatory responses within the lung. The role of SP-D in the development of allergen-induced airway inflammation and hyperresponsiveness (AHR) is not well defined. SP-D levels progressively increased up to 48 hours after allergen challenge of sensitized mice and then subsequently decreased. The levels of SP-D paralleled the development of airway eosinophilia and AHR. To determine if this association was functionally relevant, mice were administered rat SP-D (rSP-D) intratracheally. When given to sensitized mice before challenge, AHR and eosinophilia were reduced by rSP-D in a dose-dependent manner but not by mutant rSP-D. rSP-D administration resulted in increased levels of interleukin (IL)-10, IL-12, and IFN-gamma in bronchoalveolar lavage fluid and reduced goblet cell hyperplasia. Culture of alveolar macrophages together with SP-D and allergen resulted in increased production of IL-10, IL-12, and IFN-gamma. These results indicate that SP-D can (negatively) regulate the development of AHR and airway inflammation after airway challenge of sensitized mice, at least in part, by modulating the function of alveolar macrophages.
authors.affiliation: Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miyahara
authors.forename: Yeong-Ho
authors.initials: YH
authors.lastname: Rha
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Yang
authors.forename: Anthony
authors.initials: A
authors.lastname: Joetham
authors.forename: Taku
authors.initials: T
authors.lastname: Kodama
authors.forename: Annette M
authors.initials: AM
authors.lastname: Balhorn
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Catherine
authors.initials: C
authors.lastname: Duez
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Evans
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants