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 (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.


CONCLUSIONS
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.
Brandt
Eric B
EB
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Mingler
Melissa K
MK
Stevenson
Michelle D
MD
Wang
Ning
N
Khurana Hershey
Gurjit K
GK
Whitsett
Jeffrey A
JA
Rothenberg
Marc E
ME
D000293:Adolescent; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054414:Chemokine CCL17 / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009299:Nasal Provocation Tests; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics* / Q000276:immunology*; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D054414:Chemokine CCL17; D007074:Immunoglobulin G; D037663:Pulmonary Surfactant-Associated Protein D; D007073:Immunoglobulin E