| First Author | Fakih D | Year | 2015 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 309 |
| Issue | 11 | Pages | L1333-43 |
| PubMed ID | 26432866 | Mgi Jnum | J:233085 |
| Mgi Id | MGI:5780765 | Doi | 10.1152/ajplung.00090.2015 |
| Citation | Fakih D, et al. (2015) Protective effects of surfactant protein D treatment in 1,3-beta-glucan-modulated allergic inflammation. Am J Physiol Lung Cell Mol Physiol 309(11):L1333-43 |
| abstractText | 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. |
