Expression Of Surfactant Protein A In Human Nasal Epithelial Cells After Infection With Rhinovirus C In The Presence of Histamine

The nasal airway is the first barrier for inhaled pathogens. Rhinovirus is the commonest infection, and RV-C the most virulent strain. Surfactant protein A (SP-A) is a critical innate immune molecule for the lower airway, but its function in the upper airway is not well characterized. We hypothesized that: 1) RV-C binding to sinonasal epithelia (SNEC) is enhanced with histamine, 2) SP-A is expressed in SNEC, 3) SP-A levels are upregulated after RV-C infection. SP-A humanized transgenic (hTG) mice or knockouts were used to investigate expression of SP-A in mouse sinonasal tissues. SNEC isolated from chronic rhinosinusitis (CRS) patients, cultured in air-liquid interface (ALI), and infected apically (4, 24 and 48h) with GFP-RVC or vehicle in presence or absence of basolateral histamine. RVC binding and replication were assessed with fluorescence microscopy and qRT-PCR. SP-A mRNA and protein measured by qRT-PCR and western blot (WB). SP-A protein and mRNA were expressed in nasal tissues from CRS patients, differentiated ALI SNEC and in nasal tissues of SP-A hTG mice. RVC binding and replication was enhanced when histamine was present compared to basal conditions. SP-A mRNA and protein increased during RVC binding at 4h but decreased 48h post infection. RV-C binding was increased after SNEC exposure to histamine, suggesting that allergic disorders may enhance RV-C infection in vivo. SP-A was expressed and upregulated after 4 hrs of infections, but decreased at 48 hrs suggesting a novel role in the sinonasal innate immunity responses to rhinovirus infections.