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

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 (Met¹¹Thr) 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_H2-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_H2 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.

Key words: Allergy, lung, surfactant protein D, polymorphism, eosinophil, IL-13, Aspergillus, endotoxin

Abbreviations used: BALF, Bronchoalveolar lavage fluid, PAS, Periodic acid-Schiff, SNP, Single nucleotide polymorphism, SP, Surfactant protein, Sftpd^−/−, Surfactant protein D gene–deficient mice, TARC, Thymus and activation-regulated chemokine