Surfactant protein D expression in chronic rhinosinusitis patients and immune responses in vitro to Aspergillus and Alternaria in a nasal explant model

Abstract

Objectives/Hypothesis: Common fungi have been implicated in the pathogenesis of chronic rhinosinusitis (CRS) with eosinophilic mucus (EMCRS). Surfactant protein (SP)-D plays an important role in the immune response to Aspergillus fumigatus in the lungs. We sought to determine whether SP-D is expressed in nasal mucosa and investigated the response of SP-D in vitro to fungal allergens. Study Design and Methods: 1) Nasal biopsies from 59 CRS and EMCRS patients, stratified into allergic fungal sinusitis (AFS), nonallergic fungal eosinophilic sinusitis (NAFES), and nonallergic nonfungal eosinophilic sinusitis (NANFES) were studied by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunostaining and enzyme-linked immunosorbent assay (ELISA). 2) Nasal tissue from three CRS and three NANFES patients was cultured with fungal allergens in a nasal explant in vitro model for 24 hours at increasing concentrations and mRNA SP-D secreted SP-D protein levels in response to the fungi determined by qRT-PCR and ELISA. Results: Staining for SP-D was detected in the submucosal glands from the nasal biopsies in all patient groups except for AFS. By ELISA, SP-D was undetectable in AFS and decreased in NAFES, NANFES, and CRS compared with controls. CRS patients in vitro cultured with Aspergillus and Alternaria allergens in a nasal tissue explant model induced up-regulation of SP-D by qRT-PCR. In contrast, NANFES nasal tissue explants cultured with Aspergillus allergens induced down-regulation of SP-D. Conclusions: We report for the first time the expression of SP-D in both diseased and normal nasal mucosa. SP-D expression in CRS patients is up-regulated by fungal allergens in an in vitro model. These results may provide potential novel therapy for treatment of CRS.