Matching Items (1)
Filtering by
- All Subjects: Chronic Rhinosinusitis
- Creators: Sandrin, Todd R.
Description
The Surfactant Protein-A family of proteins have long been observed to allocate immune responses in the lungs, although recent evidence has surfaced which suggests similar mechanisms involving these proteins may occur in the sinonasal epithelia. In this study, the regulatory effects of SP-A on the production of Mucin5AC (mucus) in the sinuses of wild-type (control) and endogenous SP-A knock-out mice were investigated. The effects of human transgenic SP-A knock-in polymorphisms 223Gln (“risk” allele) and 223Lys (“non-risk” allele) on Mucin5AC production were also examined. It was theorized that SP-A optimally regulates Mucin5AC production and thereby some degree of innate immunity. Through inhibition of the SP-A gene, it was hypothesized that an increase in mucosal response would be observed in the endogenous SP-A knock-out samples. Upon examination, these in vivo samples consistently showed an increase in Mucin5AC production upon challenge with Pseudomonas aeruginosa strain K when compared to wild-type sets of the same treatment. The upregulation observed in the knock-out samples likely represented an ineffective mucosal response to unchecked bacterial replication in the absence of lipopolysaccharide-competitive SP-A aggregates. Mucin5AC upregulation was also observed in the 223Lys (“non-risk” allele) samples, although expression directed by this allelic variant is considered to characterize a healthy response to bacterial aggression, as the recognition/binding site on the carbohydrate domain of this polymorphism allows the effective aggregation of SP-A, which thereby promotes primary immune response in infected sinonasal tissue. Further studies will elucidate the specific molecular pathways leading to inflammatory and immune responses in the sinonasal epithelia, research which might, in the future, permit the development of novel diagnostic and therapeutic strategies in the clinical setting.
ContributorsBombar, Dan (Author) / Noutsios, George T. (Thesis director) / Sandrin, Todd R. (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05