Innate and adaptive mediators in cystic fibrosis and allergic fungal rhinosinusitis.
BACKGROUND
Surfactant-associated proteins (SP) A and D are both innate immunity mediators and produced in normal and diseased sinus mucosa. Cystic fibrosis (CF) is associated with Th1 adaptive inflammation whereas allergic fungal rhinosinusitis (AFRS) is associated with Th2 adaptive inflammation. The purpose of this study is to show and quantify the presence of SP A, SP D, tumor necrosis factor (TNF) alpha, (a Th1 marker), and eotaxin (a Th2 marker) in normal and diseased sinus mucosa.


METHODS
Intraoperative sinus mucosal biopsy specimens from human volunteers were obtained during endoscopic sinus surgery for CF (n = 4), AFRS (n = 10), and normal controls (CTLs; n = 4). Specimens were evaluated for presence and quantity of SP A, SP D, and TNF-alpha using Western blot with semiquantitative immunoblot analysis. Eotaxin was quantified using ELISA immunoassay. Results were standardized and reported as picograms of mediator per microgram of total protein.


RESULTS
SP A, SP D, and TNF-alpha levels in CF tissue extracts were 2-10 times higher than levels in AFRS tissue (with SP D and TNF-alpha reaching statistical significance) but CF tissue was not significantly higher than CTL tissue. SP A, SP D, and TNF-alpha were not significantly elevated in AFRS. Eotaxin showed elevated levels in CF and AFRS when compared with CTLs (p = 0.03 and 0.003, respectively).


CONCLUSIONS
SP D and TNF-alpha are significantly increased in CF compared with AFRS, suggesting activation of both innate immunity and Th1-mediated inflammation and potential correlation between SPs and downstream adaptive immune responses.
Skinner
Margaret L
ML
Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA. margaret.skinner@childrens.harvard.edu
Schlosser
Rodney J
RJ
Lathers
Deanne
D
Neal
Jeffrey G
JG
Woodworth
Bradford A
BA
Hall
Jeffrey
J
Newton
Danforth A
DA
Baatz
John E
JE
D054413:Chemokine CCL11 / Q000378:metabolism; D003550:Cystic Fibrosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005656:Fungal Proteins / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System; D007113:Immunity, Innate; D007249:Inflammation; D008954:Models, Biological; D009092:Mucous Membrane; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D020545:Respiratory Mucosa / Q000382:microbiology*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000382:microbiology*; D018417:Th1 Cells; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054413:Chemokine CCL11; D005656:Fungal Proteins; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha