Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 309, Issue 11, Pages L1333-L1343Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00090.2015
Keywords
surfactant protein D; 1,3-beta-glucan; allergic asthma; mouse model; ovalbumin
Categories
Funding
- Danish Strategic Research Council, Center of COPD research
- Lundbeck Foundation [R5-2006-446] Funding Source: researchfish
- Medical Research Council [1085361] Funding Source: researchfish
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Surfactant protein D (SP-D) is a pulmonary collectin important in lung immunity. SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin (OVA)-and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. beta-Glucans are a diverse group of polysaccharides previously suggested to serve as fungal ligands for SP-D. We set out to investigate if SP-D could interact with 1,3-beta-glucan and attenuate allergic pulmonary inflammation in the presence of 1,3-beta-glucan. Allergic airway disease was induced in Sftpd(-/-) and Sftpd(-/-) mice by OVA sensitization and subsequent challenge with OVA, 1,3-beta-glucan, or OVA/1,3-beta-glucan together. Mice in the combined treatment group were further treated with a high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct interaction between SP-D and 1,3-beta-glucan. OVA-induced mucous cell metaplasia was increased in Sftpd(-/-) mice, supporting previously reported protective effects of endogenous SP-D in allergy. OVA-induced parenchymal CCL11 levels and eosinophilic infiltration in bronchoalveolar lavage were unaffected by 1,3-beta-glucan, but were reversed with rfhSP-D treatment. 1,3-beta-Glucan treatment did, however, induce pulmonary neutrophilic infiltration and increased TNF-alpha levels in bronchoalveolar lavage, independently of OVA-induced allergy. This infiltration was also reversed by treatment with rfhSP-D. 1,3-beta-Glucan reduced OVA-induced mucous cell metaplasia, T helper 2 cytokines, and IFN-gamma production. rfhSP-D treatment further reduced mucous metaplasia and T helper 2 cytokine secretion to background levels. In summary, rfhSP-D treatment resulted in attenuation of both allergic inflammation and 1,3-beta-glucan-mediated neutrophilic inflammation. Our data suggest that treatment with high-dose SP-D protects from mold-induced exacerbations of allergic asthma.
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