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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:121

Article

Brandt, Eric B.¹  Mingler, Melissa K.¹  Stevenson, Michelle D.^3,4  Wang, Ning¹  Hershey, Gurjit K. Khurana¹  Whitsett, Jeffrey A.²  Rothenberg, Marc E.¹ 

[1] Univ Cincinnati, Coll Med, Div Allergy & Immunol, Dept Pediat,Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[2] Univ Cincinnati, Coll Med, Div Neonatol & Pulm Biol, Dept Pediat,Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[3] Akron Childrens Hosp, Div Emergency Med, Akron, OH USA

[4] Northeastern Ohio Univ Coll Med & Pharm, Akron, OH USA

关键词: allergy;    lung;    surfactant protein D;    polymorphism;    eosinophil;    IL-13;    Aspergillus;    endotoxin;   

DOI  :  10.1016/j.jaci.2008.02.011

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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