Protective effects of surfactant protein D (SP-D) treatment in 1,3-beta-glucan-modulated allergic inflammation

Tidsskriftartikel - 2015


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 brochoalveolar lavage (BAL) 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 BAL, 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, Th2 cytokines and IFN-gamma production. rfhSP-D treatment further reduced mucous metaplasia and Th2 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


Fakih D, Pilecki B, Schlosser A, Jepsen C, Thomsen L, Ormhøj M, Watson A, Madsen J, Clark H, Barfod KK, Hansen S, Marcussen N, Jounblat R, Chamat S, Holmskov U, Sørensen G. Protective effects of surfactant protein D (SP-D) treatment in 1,3-beta-glucan-modulated allergic inflammation. American Journal of Physiology Lung Cell Molecular Physiology 2015;309(11):L1333-L1343.
doi: 10.1152/ajplung.00090.2015

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