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Am J Physiol Lung Cell Mol Physiol (October 3, 2003). doi:10.1152/ajplung.00380.2002
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00380.2002v1
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Submitted on November 7, 2002
Accepted on October 1, 2003

Environmental Oxygen Tension Affects Phenotype in Cultured Bone Marrow Derived Macrophages

Jean C. Pfau1*, Jordan C. Schneider1, Amy J. Archer1, Jami Sentissi1, Francisco J. Leyva1, and Jennifer Cramton1

1 Center for Enviornmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT, USA

* To whom correspondence should be addressed. E-mail: jpfau{at}selway.umt.edu.

This study tested the hypothesis that the unique phenotype of alveolar macrophages (AM) is maintained through adaptation to the relatively high oxygen partial pressure (PO2) of the lung, through modification of redox sensitive transcription factors. Balb/c mouse bone marrow derived macrophages (BMC) were differentiated under different PO2, and compared functionally to AM and peritoneal macrophages (PM). BMC differentiated in normoxia (PO2 140 mmHg, BMChigh) were similar to AM in having low phagocytic and antigen presenting cell (APC) activities. However, BMC grown in low oxygen tension as found in other tissues (<40 mmHg, BMClow), were better phagocytes and APCs, similar to PM. BMChigh were more oxidative intracellularly than BMClow, based on oxidation of dichloro-fluorescein and higher GSSG:GSH ratios, despite having more glutathione. Finally, lipopolysaccharide-induced NF-{kappa}B translocation, measured by laser scanning cytometry, was reduced in BMChigh and AM, compared to BMClow and PM, respectively. These data suggest that regulation of the AM phenotype may occur, at least in part, via inhibition of NF-{kappa}B by the unique redox environment.




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