Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 121, Issue 5, Pages 1140-1147Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2008.02.011
Keywords
allergy; lung; surfactant protein D; polymorphism; eosinophil; IL-13; Aspergillus; endotoxin
Categories
Funding
- NHLBI NIH HHS [HL-63329, HL-076383, P01 HL076383, R01 HL063329] Funding Source: Medline
- NIAID NIH HHS [R01 AI057803, R01 AI42242, AI057803, R01 AI042242] Funding Source: Medline
- NIAMS NIH HHS [R01 AR042242] Funding Source: Medline
- NICHD NIH HHS [T32 HD43005-01, T32 HD043005] Funding Source: Medline
- NIEHS NIH HHS [T32 ES10957-03, T32 ES010957] Funding Source: Medline
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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.
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