Molecular & Cellular Biology Program email@example.com University of Iowa 357 Medical Research Center Iowa City, IA 52242-1182 Phone: 319-335-7748 Fax: 319-335-7656
To better understand the biology of neutrophilic inflammation and mechanisms of NADPH oxidase in intracellular signaling in neutrophils
The Moreland laboratory has two primary ongoing areas of investigation both related to better understanding the biology of neutrophilic inflammation. One of our broad areas of interest is investigation of mechanisms of neutrophil priming by both inflammatory (TNF-α) and infectious (endotoxin) stimuli. These studies seek to define mechanisms of NADPH oxidase-derived signaling under basal and primed conditions that are relevant to maintaining the host inflammatory balance. Using confocal microscopy and basic biochemistry, neutrophil responses to pathophysiologically relevant concentrations of TNF-α and endotoxin are characterized in freshly isolated human neutrophils. A murine model of in vivo neutrophil priming is also under investigation. One focus within this project explores the role of the H+/Cl- antiporter, ClC-3, in neutrophil function. Our data strongly suggest that this antiporter serves a charge neutralizing function for the NADPH oxidase in endosomal vesicles.
The second broad focus area is host pathogen interactions in the lung. Currently there are two areas of active investigation in our lab. 1) Francisella tularensis interactions with lung epithelium and endothelium including understanding mechanisms of pathogen entry into host cells and effects of bacterial invasion on neutrophil transmigration and function. 2) Neutrophil-endothelial interactions with S. pneumoniae. These studies focus on alterations in neutrophils occurring as a result of transendothelial migration in response to intact bacteria. Both bacterial and endothelial factors that elicit neutrophil phenotypic changes are explored.
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