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

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

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.

Animals, Chemokine CCL11, Cytokines, Female, Humans, Hypersensitivity, Immunoglobulin E, Inflammation, Ligands, Metaplasia, Mice, Inbred C57BL, Microbiota, Ovalbumin, Protective Agents, Pulmonary Alveoli, Pulmonary Surfactant-Associated Protein D, Respiratory Hypersensitivity, beta-Glucans, Journal Article, Research Support, Non-U.S. Gov't
1040-0605
L1333-1343
Fakih, Dalia
6b3cca28-b1a8-42c3-be60-0b5fd32360ee
Pilecki, Bartosz
2a7baa70-6251-41ab-9509-4b171cdfb9b0
Schlosser, Anders
37911406-2ff0-4ef1-9f01-c03576a9dd98
Jepsen, Christine S.
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Thomsen, Laura K.
cb3851c5-9d69-4ba8-af13-1707567b4868
Ormhøj, Maria
c4bcd60d-c264-438c-af86-d6416ced2af3
Watson, Alastair
9eb79329-8d32-4ed4-b8b9-d720883e8042
Madsen, Jens
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Clark, Howard W.
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Barfod, Kenneth K.
c1b6364d-fceb-4484-8eb4-b14d7115499b
Hansen, Soren
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Marcussen, Niels
ac3560a9-96ee-42c6-b73a-b096c7b4463e
Jounblat, Rania
51c34e74-8d8e-44cc-8b1a-dc2e955a2e5a
Chamat, Soulaima
8ce7f939-10d8-4ddf-9ea9-57d1f95fb393
Holmskov, Uffe
8a55aecd-694c-4d61-849b-9cf32da8ba39
Sorensen, Grith L.
25ac3a15-3fc9-4dab-9fa5-caf89893b845
Fakih, Dalia
6b3cca28-b1a8-42c3-be60-0b5fd32360ee
Pilecki, Bartosz
2a7baa70-6251-41ab-9509-4b171cdfb9b0
Schlosser, Anders
37911406-2ff0-4ef1-9f01-c03576a9dd98
Jepsen, Christine S.
7d086768-a5b3-4d0e-880a-e69d5979039e
Thomsen, Laura K.
cb3851c5-9d69-4ba8-af13-1707567b4868
Ormhøj, Maria
c4bcd60d-c264-438c-af86-d6416ced2af3
Watson, Alastair
9eb79329-8d32-4ed4-b8b9-d720883e8042
Madsen, Jens
b5d8ae35-00ac-4d19-930e-d8ddec497359
Clark, Howard W.
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Barfod, Kenneth K.
c1b6364d-fceb-4484-8eb4-b14d7115499b
Hansen, Soren
a97e00fd-2d4a-4959-ad73-43a7f8744303
Marcussen, Niels
ac3560a9-96ee-42c6-b73a-b096c7b4463e
Jounblat, Rania
51c34e74-8d8e-44cc-8b1a-dc2e955a2e5a
Chamat, Soulaima
8ce7f939-10d8-4ddf-9ea9-57d1f95fb393
Holmskov, Uffe
8a55aecd-694c-4d61-849b-9cf32da8ba39
Sorensen, Grith L.
25ac3a15-3fc9-4dab-9fa5-caf89893b845

Fakih, Dalia, Pilecki, Bartosz, Schlosser, Anders, Jepsen, Christine S., Thomsen, Laura K., Ormhøj, Maria, Watson, Alastair, Madsen, Jens, Clark, Howard W., Barfod, Kenneth K., Hansen, Soren, Marcussen, Niels, Jounblat, Rania, Chamat, Soulaima, Holmskov, Uffe and Sorensen, Grith L. (2015) Protective effects of surfactant protein D treatment in 1,3-β-glucan-modulated allergic inflammation. American Journal of Physiology: Lung Cellular and Molecular Physiology, 309 (11), L1333-1343. (doi:10.1152/ajplung.00090.2015).

Record type: Article

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.

Full text not available from this repository.

More information

Accepted/In Press date: 18 September 2015
e-pub ahead of print date: 1 December 2015
Published date: 1 December 2015
Additional Information: Copyright © 2015 the American Physiological Society.
Keywords: Animals, Chemokine CCL11, Cytokines, Female, Humans, Hypersensitivity, Immunoglobulin E, Inflammation, Ligands, Metaplasia, Mice, Inbred C57BL, Microbiota, Ovalbumin, Protective Agents, Pulmonary Alveoli, Pulmonary Surfactant-Associated Protein D, Respiratory Hypersensitivity, beta-Glucans, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 418768
URI: https://eprints.soton.ac.uk/id/eprint/418768
ISSN: 1040-0605
PURE UUID: daa4db9d-4ba1-4e2f-b0ad-17f116584438
ORCID for Jens Madsen: ORCID iD orcid.org/0000-0003-1664-7645

Catalogue record

Date deposited: 21 Mar 2018 17:30
Last modified: 14 Mar 2019 01:39

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