Title: Surfactant protein D alters allergic lung responses in mice and human subjects.
Authors: Brandt, Eric B; Mingler, Melissa K; Stevenson, Michelle D; Wang, Ning; Khurana Hershey, Gurjit K; Whitsett, Jeffrey A; Rothenberg, Marc E
Published In J Allergy Clin Immunol, (2008 May)
Abstract: Surfactant protein (SP) D has been proposed to be protective in allergic airway responses.We aimed to determine the effect of SP-D deficiency on murine and human airway allergy.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.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.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.
PubMed ID: 18355911
MeSH Terms: Adolescent; Allergens/immunology; Animals; Asthma/immunology; Bronchoalveolar Lavage Fluid/cytology; Bronchoalveolar Lavage Fluid/immunology; CD4-Positive T-Lymphocytes/immunology; Chemokine CCL17/biosynthesis; Child; Child, Preschool; Female; Flow Cytometry; Humans; Immunoglobulin E/immunology; Immunoglobulin G/immunology; Lung/immunology*; Lung/metabolism; Macrophages/immunology; Macrophages/metabolism; Male; Mice; Mice, Mutant Strains; Nasal Provocation Tests; Neutrophils/immunology; Neutrophils/metabolism; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Pulmonary Surfactant-Associated Protein D/genetics*; Pulmonary Surfactant-Associated Protein D/immunology*; Respiratory Function Tests; Respiratory Hypersensitivity/immunology*; Respiratory Mucosa/immunology; Respiratory Mucosa/metabolism