Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice.
BACKGROUND
Surfactant protein D (SP-D) is involved in the innate immunity within the lung and may have important roles in modulating the inflammatory process of asthma.


OBJECTIVE
To examine the potential immunomodulating role of SP-D on the allergic response in mice, and its interaction with the alveolar macrophages (AMs) during allergic inflammation.


METHODS
A recombinant 60 kDa fragment of human SP-D (rfh SP-D), Survanta, and budesonide were administrated, respectively, to Der p-sensitive BALB/c mice before or after allergen challenge (AC). Total and differential cell counts, levels of cytokines in bronchoalveolar lavage fluids(BALFs), and levels of Der p-specific IgE and IgG1 antibodies in sera, were assayed. The production of nitric oxide (NO), and inducible NO synthase (iNOS) expression, in AMs, were determined by ELISA and RT-PCR, respectively.


RESULTS
Instillation of rfh SP-D to sensitized mice 6 h after AC (therapeutic), but not 24 h before AC (preventive), markedly reduced infiltration of eosinophils, and also reduced levels of IL-4, IL-5, eotaxin, and TNF-alpha but elevated levels of IFN-gamma in the BALF. These effects were comparable with those obtained with budesonide treatment, whereas Survanta did not have a suppressive effect, either before or after AC. There was significant inhibition of NO production in the rfh SP-D pre-treated AMs of allergen-sensitized mice, but not in naive mice.


CONCLUSIONS
These results indicate that rfh SP-D has a therapeutic effect on allergen-induced bronchial inflammation, and that this might be because of its inhibitory effect on NO and TNF-alpha production by AMs, and it thus prevents the development of T-helper type 2 cytokine response.
Liu
C-F
CF
Institutes of Basic Medicine and Biochemistry, National Cheng Kung University, Tainan, Taiwan. a122@mail.ncku.edu.tw
Chen
Y-L
YL
Shieh
C-C
CC
Yu
C-K
CK
Reid
K B M
KB
Wang
J-Y
JY
D000485:Allergens / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001688:Biological Products / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D019819:Budesonide / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000276:immunology; D002631:Chemotactic Factors, Eosinophil / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology* / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000276:immunology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000485:Allergens; D000893:Anti-Inflammatory Agents; D039741:Antigens, Dermatophagoides; D001688:Biological Products; C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D015848:Interleukin-5; D008070:Lipopolysaccharides; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D009569:Nitric Oxide; D019819:Budesonide; D007371:Interferon-gamma; C072197:beractant