Effect of Smoke Exposure and Ethanol Ingestion on Anti-Pneumococcal Host Defenses

dc.contributor.advisorGentry-Nielsen, Martha J.en_US
dc.contributor.authorVander Top, Elizabeth Anneen_US
dc.contributor.cuauthorVander Top, Elizabeth Anneen_US
dc.degree.committeePreheim, Laurel C.en_US
dc.degree.committeeLister, Philip D.en_US
dc.degree.committeeSwanson, Patrick C.en_US
dc.degree.committeeJerrells, Tomen_US
dc.degree.disciplineMedical Microbiology and Immunology (graduate program)en_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.levelPhD (Doctor of Philosophy)en_US
dc.degree.namePh.D. in Medical Microbiology and Immunologyen_US
dc.description.abstractAlcohol abusers and smokers are more susceptible to the development of respiratory tract infections caused by Streptococcus pneumoniae, the pneumococcus.To investigate the effect of smoke exposure and EtOH ingestion on host defenses against the pneumococcus, rats were exposed to the smoke generated from 30 reference cigarettes for one hour twice daily for either 8 or 12 weeks (smokeexposed), or to room air (sham-exposed). For the final one or five weeks of smoke exposure the rats were switched from their normal rat chow to a liquid diet containing 0%, 16%, 26%, or 36% EtOH calories. For certain experiments, rats were fed the 36% EtOH diet ad libitum or pair-fed a liquid control diet that did not contain alcohol. Consumption of the 26% or 36% EtOH diets alone resulted in increased movement of pneumococci from the rats' nasopharynx into the lungs. This EtOH induced defect in host mucociliary defense was dose dependent, and was intensified by concurrent smoke exposure. The increased movement of pneumococci into the lungs of the smoke-exposed and EtOH-fed rats correlated to deficits in the ability of their ciliated tracheal epithelial cells to increase their ciliary beat frequency in response to an in vitro stimulus. To investigate the effect of concurrent smoke exposure and EtOH ingestion on pulmonary polymorphonuclear leukocyte (PMN) functions an in vivo phagocytosis assay was developed. Neither PMN recruitment to the lung nor PMN phagocytosis of pneumococci was impaired by separate or concurrent smoke exposure and EtOH ingestion. However, one week of EtOH ingestion significantly reduced the percentage of pneumococci killed within the rats’ lungs in an in vivo bactericidal assay. Surprisingly, this EtOH-induced defect was reversed by concurrent smoke exposure, although smoke exposure alone did not increase intrapulmonary pneumococcal clearance. Pulmonary chemokine levels of two chemotactic chemokines were significantly increased by concurrent smoke exposure and EtOH ingestion, even though these differences did not result in alterations in PMN recruitment to the lung. EtOH ingestion alone significantly decreased systemic levels of cytokine-induced neutrophil chemoattractant-1 (CINC-1), which may help to explain alterations in PMN activation and pneumococcal killing in the EtOH-ingesting host. These results suggest that concurrent smoke exposure and EtOH ingestion increase susceptibility to pneumocccal infections by impairing effective mucociliary and PMN clearance of the organisms from the lungs. Further studies will be necessary to determine whether these defects in pulmonary clearance arise from alterations in chemokine-induced activation.en_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.description.pagesxiii, 141 pagesen_US
dc.publisherCreighton Universityen_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.rights.holderElizabeth Anne Vander Topen_US
dc.subject.meshRisk Factorsen_US
dc.subject.meshStreptococcus pneumoniaeen_US
dc.titleEffect of Smoke Exposure and Ethanol Ingestion on Anti-Pneumococcal Host Defensesen_US
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