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. β-
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-β-glucan and attenuate allergic
pulmonary inflammation in the presence of 1,3-β-glucan. Allergic airway disease was induced in Sftpd(-/-) and Sftpd(+/+) mice by OVA sensitization and subsequent challenge with OVA, 1,3-β-glucan, or OVA/1,3-β-
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-β-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-β-glucan, but were reversed with rfhSP-D treatment. 1,3-β-Glucan treatment did, however, induce pulmonary neutrophilic infiltration and increased TNF-α levels in bronchoalveolar lavage, independently of OVA-induced
allergy. This infiltration was also reversed by treatment with rfhSP-D. 1,3-β-Glucan reduced OVA-induced mucous cell
metaplasia, T helper 2
cytokines, and IFN-γ 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-β-glucan-mediated neutrophilic
inflammation. Our data suggest that treatment with high-dose
SP-D protects from mold-induced exacerbations of allergic
asthma.