Date of Graduation
The leading cause of death among cystic fibrosis (CF) patients is progressive lung disease characterized by an early, sustained inflammation, chronic infection by mucoid strains of P. aeruginosa, and subsequent bronchiectasis. The connection between defective CFTR and the apparent pathophysiology of the CF lung remains unclear. Understanding this connection is of critical importance in developing strategies that temper the respiratory inflammation in CF and prevent P. aeruginosa colonization of the airways. The goal of this dissertation was to provide new insight concerning the immunology and infection of the CF lung by investigating the following: (1) the effect of alginate on the invasion of CF respiratory epithelial cells by clinical isolates of P. aeruginosa; (2) the levels of IL-8 produced by both CF and normal respiratory epithelial cells under uninduced and induced conditions; (3) the expression of additional proteins that interact with CFTR in respiratory epithelia, namely NHE-RF; and (4) the development of a laboratory test that facilitates the identification and study of P. aeruginosa biofilms. Using transformed CF respiratory epithelial cell lines we demonstrated that mucoid P. aeruginosa clinical isolates associate with and invade CF respiratory epithelial cells less efficiently than non-mucoid P. aeruginosa. Further studies of CF, normal, and corrected CF respiratory epithelial cell lines indicated that (1) interleukin-8 (IL-8) message and protein levels were reduced in CF respiratory epithelial cells; and (2) the sodium/hydrogen exchange regulatory factor (NHE-RF), previously shown to interact with CFTR in vitro, was not expressed in either CF, normal, or corrected CF respiratory epithelial cell lines. Finally, we demonstrated that the paraffin wax baiting system with Czapek's minimal salts medium is useful for the growth and identification of P. aeruginosa using paraffin as sole carbon source. Our studies are significant because they have furthered our understanding of the interaction between the CF host immune response and the pathophysiology of cystic fibrosis before and after bacterial infection with Pseudomonas aeruginosa. Reduced 1L-8 expression by CF respiratory epithelial cells and reduced epithelial cell invasion may facilitate the survival of mucoid P. aeruginosa strains at the airway surface.
Drummond Massengale, Andrea Rene, "The immunology and infection of the cystic fibrosis lung." (1999). Graduate Theses, Dissertations, and Problem Reports. 8787.