Surfactant protein D alters allergic lung responses in mice and human subjects

Title

Surfactant protein D alters allergic lung responses in mice and human subjects

Creator

Brandt E B; Mingler M K; Stevenson M D; Wang N; Hershey G K K; Whitsett J A; Rothenberg M E

Publisher

Journal of Allergy and Clinical Immunology

Date

2008
2008-05

Description

Background: Surfactant protein (SP) D has been proposed to be protective in allergic airway responses. Objective: We aimed to determine the effect of SP-D deficiency on murine and human airway allergy. Methods: Immunologic responses of SP-D gene-deficient mice (Sftpd(-/-)) at baseline and after 4 intranasal Aspergillus fumigatus exposures were assessed. In addition, the significance of a single nucleotide polymorphism (Met(11)Thr) in the human SP-D gene (known to decrease SP-D function) was investigated. Results: Macrophage and neutrophil bronchoalveolar lavage fluid levels and large airway mucus production were increased in naive Sftpd(-/-) mice in association with increased lung CCL17 levels and CD4(+) T cell numbers. T(H)2-associated antibody levels (IgG1 and IgE) were significantly lower in 4- to 5-week-old Sftpd(-/-) mice (P <.05). Accordingly, naive Sftpd(-/-) splenocytes released significantly less IL-4 and IL-13 on anti-CD3/CD28 stimulation (P <.01). After intranasal allergen exposures, a modest decrease in bronchoalveolar lavage fluid eosinophilia and IL-13 levels was observed in Sftpd(-/-) mice compared with values seen in wild-type mice in association with decreased airway resistance (P <.01). A single nucleotide polymorphism in the SFTPD gene, affecting SP-D levels and pathogen binding, was associated with decreased atopy in black subjects and potentially lower asthma susceptibility in white subjects. Conclusion: Sftpd(-/-) mice have an impaired systemic T(H)2 response at baseline and reduced inflammation and airway responses after allergen exposure. Translational studies revealed that a polymorphism in the SFTPD gene was associated with lower atopy and possibly asthma susceptibility. Taken together, these results support the hypothesis that SP-D-dependent innate immunity influences atopy and asthma.

Subject

inflammation; asthma; Immunology; polymorphism; lung; Allergy; endotoxin; Aspergillus; deficient mice; Allergy; aspergillus-fumigatus; d gene; emphysema; eosinophil; hygiene hypothesis; IL-13; sftpd gene; sp-a; surfactant protein D

Format

Journal Article or Conference Abstract Publication

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1140-1147

Issue

5

Volume

121

Citation

Brandt E B; Mingler M K; Stevenson M D; Wang N; Hershey G K K; Whitsett J A; Rothenberg M E, “Surfactant protein D alters allergic lung responses in mice and human subjects,” NEOMED Bibliography Database, accessed November 26, 2021, https://neomed.omeka.net/items/show/8707.

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