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Am J Physiol Lung Cell Mol Physiol. 2015 Dec 1;309(11):L1333-43. doi: 10.1152/ajplung.00090.2015. Epub 2015 Oct 2.

Protective effects of surfactant protein D treatment in 1,3-β-glucan-modulated allergic inflammation.

Author information

1
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; Department of Biology, Faculty of Sciences II, Lebanese University, Fanar, Lebanon; Laboratory of Immunology, Faculty of Public Health, Lebanese University, Fanar, Lebanon;
2
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;
3
Department of Child Health, Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom;
4
Department of Child Health, Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom; National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom;
5
National Research Centre for the Working Environment, Copenhagen, Denmark; and.
6
Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.
7
Department of Biology, Faculty of Sciences II, Lebanese University, Fanar, Lebanon; Laboratory of Immunology, Faculty of Public Health, Lebanese University, Fanar, Lebanon;
8
Laboratory of Immunology, Faculty of Public Health, Lebanese University, Fanar, Lebanon;
9
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; glsorensen@health.sdu.dk.

Abstract

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.

KEYWORDS:

1,3-β-glucan; allergic asthma; mouse model; ovalbumin; surfactant protein D

PMID:
26432866
DOI:
10.1152/ajplung.00090.2015
[Indexed for MEDLINE]
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