Jessica G. Moreland, MD
Research Profile

Research Interests:

Ongoing studies in our laboratory focus on understanding some of the early components of the innate immune response to bacterial pathogens in the lung. We are specifically interested in neutrophil-endothelial cell interactions, and neutrophil transendothelial migration during the onset of pneumonia caused by Streptococcus pneumoniae. Pneumococcal pneumonia is the leading cause of community acquired pneumonia in adults and children and pneumonia caused by this organism is frequently very severe with significant morbidity. We have developed an in vitro model of neutrophil transmigration that examines human PMN migration in the luminal to abluminal direction across a monolayer of pulmonary microvascular endothelial cells in response to intact bacterial stimuli at the abluminal surface of the endothelial monolayer.

Current investigations explore three main questions: 1) What bacterial products are involved in eliciting neutrophil transmigration and how do they interact with the endothelium, 2) what is the role of the vascular endothelium in transducing signals from pathogens, and 3) How is the neutrophil functionally changed during the process of transmigration?

A second project in the laboratory in collaboration with Dr. Fred Lamb in the department of Pediatrics focuses on the role of ClC-3, an anion channel, in the regulation of neutrophil oxidative function. This project has expanded to focus on several questions related to anion transport including: 1) What is the role of ClC-3 in regulation of NADPH oxidase function during PMN priming by endotoxin, 2) How does anion transport interact with cell volume regulation during cell motility?

Lab Members:

• Paige Davis (Associate in Pediatrics)
• Gail Bailey (Research Assistant)
• Jessica Hook (Research Assistant)

Affiliations:

• Department of Pediatrics
• The Inflammation Program

Model System:

In vitro cell culture model of human neutrophil migration across a monolayer of pulmonary microvascular endothelial cells in response to S. pneumoniae.

Recent Publications:

1. Moreland JG, Bailey G, Nauseef WM, Weiss JP: Organism-specific neutrophil-endothelial cell interactions in response to E. coli, S. pneumoniae, and S. aureus, Journal of Immunology 2004; 172: 426-32.
2. Moreland JG, and Bailey G: Neutrophil transendothelial migration in vitro to Streptococcus pneumoniae is pneumolysin dependent. Am J Physiol Lung Cell Mol Physiol. 2006 May; 290(5):L833-40.
3. Moreland JG, Davis AP, Bailey G, Nauseef WM, Lamb FS: Anion channels, including ClC-3, are required for normal neutrophil oxidative function, phagocytosis, and transendothelial migration. Journal of Biological Chemistry 2006 May 5;281(18):12277-88.
4. Femling JK, Cherny VV, Morgan D, Rada B, Davis AP, Czirják G, Enyedi P, England SK, Moreland JG, Ligeti E, Nauseef WM, DeCoursey TE: The Antibacterial Activity of Human Neutrophils and Eosinophils Requires Proton Channels but Not BK Channels. J Gen Physiol. 2006 May 15; [Epub ahead of print]
5. Moreland JG, Hook J, Weiss JP, Nauseef WM: Neisseria meningitides elicited neutrophil transendothelial migration is partially independent of lipooligosaccharide. In preparation.
6. Moreland JG, Davis AP, Bailey GC, Nauseef WM, Lamb FS: Neutrophil priming by endotoxin is mediated by oxidant signaling and requires anion channels. In preparation.