title: Protective effects of surfactant protein D treatment in 1,3-β-glucan-modulated allergic inflammation.
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.
authors.affiliation: 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;
authors.forename: Dalia
authors.initials: D
authors.lastname: Fakih
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pilecki
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;
authors.forename: Anders
authors.initials: A
authors.lastname: Schlosser
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;
authors.forename: Christine S
authors.initials: CS
authors.lastname: Jepsen
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;
authors.forename: Laura K
authors.initials: LK
authors.lastname: Thomsen
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;
authors.forename: Maria
authors.initials: M
authors.lastname: Ormhøj
authors.affiliation: Department of Child Health, Sir Henry Wellcome Laboratories, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom;
authors.forename: Alastair
authors.initials: A
authors.lastname: Watson
authors.affiliation: 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;
authors.forename: Jens
authors.initials: J
authors.lastname: Madsen
authors.affiliation: 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;
authors.forename: Howard W
authors.initials: HW
authors.lastname: Clark
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark; and.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Barfod
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;
authors.forename: Soren
authors.initials: S
authors.lastname: Hansen
authors.affiliation: Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Marcussen
authors.affiliation: Department of Biology, Faculty of Sciences II, Lebanese University, Fanar, Lebanon; Laboratory of Immunology, Faculty of Public Health, Lebanese University, Fanar, Lebanon;
authors.forename: Rania
authors.initials: R
authors.lastname: Jounblat
authors.affiliation: Laboratory of Immunology, Faculty of Public Health, Lebanese University, Fanar, Lebanon;
authors.forename: Soulaima
authors.initials: S
authors.lastname: Chamat
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.affiliation: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; glsorensen@health.sdu.dk.
authors.forename: Grith L
authors.identifier: http://orcid.org/0000-0002-5273-1097
authors.initials: GL
authors.lastname: Sorensen
mesh_terms: D000818:Animals; D054413:Chemokine CCL11 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D007073:Immunoglobulin E / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D008024:Ligands; D008679:Metaplasia; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects; D010047:Ovalbumin; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011509:Proteoglycans; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D037663:Pulmonary Surfactant-Associated Protein D / Q000494:pharmacology / Q000627:therapeutic use*; D012130:Respiratory Hypersensitivity / Q000150:complications; D047071:beta-Glucans / Q000378:metabolism*
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D016207:Cytokines; D008024:Ligands; D020011:Protective Agents; D011509:Proteoglycans; D037663:Pulmonary Surfactant-Associated Protein D; D047071:beta-Glucans; D007073:Immunoglobulin E; C010770:polysaccharide-K; D010047:Ovalbumin
keywords: 1,3-β-glucan; allergic asthma; mouse model; ovalbumin; surfactant protein D