Surfactant protein D regulates airway function and allergic inflammation through modulation of macrophage function.
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.
Takeda
Katsuyuki
K
Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.
Miyahara
Nobuaki
N
Rha
Yeong-Ho
YH
Taube
Christian
C
Yang
Eun-Seok
ES
Joetham
Anthony
A
Kodama
Taku
T
Balhorn
Annette M
AM
Dakhama
Azzeddine
A
Duez
Catherine
C
Evans
Amanda J
AJ
Voelker
Dennis R
DR
Gelfand
Erwin W
EW
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*
D016207:Cytokines; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants