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

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.

• Authors: Eric B Brandt, Melissa K Mingler, Michelle D Stevenson, Ning Wang, Gurjit K Khurana Hershey, Jeffrey A Whitsett, Marc E Rothenberg
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 121 Issue 5 Pg. 1140-1147.e2 (May 2008) ISSN: 1097-6825 [Electronic] United States
• PMID: 18355911 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Chemokine CCL17
• Immunoglobulin G
• Pulmonary Surfactant-Associated Protein D
• Immunoglobulin E

Topics

• Adolescent
• Allergens (immunology)
• Animals
• Asthma (immunology)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Chemokine CCL17 (biosynthesis)
• Child
• Child, Preschool
• Female
• Flow Cytometry
• Humans
• Immunoglobulin E (immunology)
• Immunoglobulin G (immunology)
• Lung (immunology, metabolism)
• Macrophages (immunology, metabolism)
• Male
• Mice
• Mice, Mutant Strains
• Nasal Provocation Tests
• Neutrophils (immunology, metabolism)
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide
• Pulmonary Surfactant-Associated Protein D (genetics, immunology)
• Respiratory Function Tests
• Respiratory Hypersensitivity (immunology)
• Respiratory Mucosa (immunology, metabolism)