Surfactant Protein D Alters Allergic Lung Responses in Mice and Human Subjects

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2008 Mar 22

PMID 18355911

Citations 26

Authors

Eric B Brandt

Melissa K Mingler

Michelle D Stevenson

Ning Wang

Gurjit K Khurana Hershey

Jeffrey A Whitsett

Marc E Rothenberg

Affiliations

Soon will be listed here.

Abstract

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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