Alterations in alveolar macrophage (AM) function during sepsis-induced hypoxia may influence tumor necrosis factor (TNF) secretion and the progression of acute lung injury. Nuclear factor (NF)-B is thought to regulate the expression of endotoxin [lipopolysaccharide (LPS)]-induced inflammatory cytokines such as TNF, and NF-B may also be influenced by changes in O₂ tension. It is thus proposed that acute changes in O₂ tension surrounding AMs alter NF-B activation and TNF secretion in these lung cells. AM-derived TNF secretion and NF-B expression were determined after acute hypoxic exposure of isolated Sprague-Dawley rat AMs. Adhered AMs (10⁶/ml) were incubated (37°C at 5% CO₂) for 2 h with LPS (Pseudomonas aeruginosa, 1 µg/ml) in normoxia (21% O₂-5% CO₂) or hypoxia (1.8% O₂-5% CO₂). AM-derived TNF activity was measured with a TNF-specific cytotoxicity assay. Electrophoretic mobility shift and supershift assays were used to determine NF-B activation and to identify NF-B isoforms in AM extracts. In addition, mRNAs for selected AM proteins were determined with RNase protection assays. LPS-exposed AMs in hypoxia had higher levels of TNF (P < 0.05) and enhanced expression of NF-B (P < 0.05); the predominant isoforms were p65 and c-Rel. Increased mRNA bands for TNF-, interleukin-1, and interleukin-1 were also observed in the hypoxic AMs. These results suggest that acute hypoxia in the lung may induce enhanced NF-B activation in AMs, which may result in increased production and release of inflammatory cytokines such as TNF.

transcription factor; nuclear factor-B; oxygen; acute lung injury; cytokines

This article has been cited by other articles:

				T. Suzuki, T. Shimizu, H.-P. Yu, Y.-C. Hsieh, M. A. Choudhry, M. G. Schwacha, and I. H. Chaudry Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage J Appl Physiol, January 1, 2007; 102(1): 163 - 168. [Abstract] [Full Text] [PDF]

				D S Urquhart, H Montgomery, and A Jaffe Assessment of hypoxia in children with cystic fibrosis Arch. Dis. Child., November 1, 2005; 90(11): 1138 - 1143. [Abstract] [Full Text] [PDF]

				C. Madjdpour, U. R. Jewell, S. Kneller, U. Ziegler, R. Schwendener, C. Booy, L. Klausli, T. Pasch, R. C. Schimmer, and B. Beck-Schimmer Decreased alveolar oxygen induces lung inflammation Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L360 - L367. [Abstract] [Full Text] [PDF]

				D. Jarrar, J. F. Kuebler, L. W. Rue III, S. Matalon, P. Wang, K. I. Bland, and I. H. Chaudry Alveolar macrophage activation after trauma-hemorrhage and sepsis is dependent on NF-kappa B and MAPK/ERK mechanisms Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L799 - L805. [Abstract] [Full Text] [PDF]

				B. V. Naidu, B. Krishnadasan, K. Byrne, A. L. Farr, M. Rosengart, E. D. Verrier, and M. S. Mulligan Regulation of chemokine expression by cyclosporine a in alveolar macrophages exposed to hypoxia and reoxygenation Ann. Thorac. Surg., September 1, 2002; 74(3): 899 - 905. [Abstract] [Full Text] [PDF]

				H. H. Hovels-Gurich, K. Schumacher, J. F. Vazquez-Jimenez, M. Qing, U. Huffmeier, B. Buding, B. J. Messmer, G. von Bernuth, and M.-C. Seghaye Cytokine balance in infants undergoing cardiac operation Ann. Thorac. Surg., February 1, 2002; 73(2): 601 - 608. [Abstract] [Full Text] [PDF]

				N. S. Chandel, W. C. Trzyna, D. S. McClintock, and P. T. Schumacker Role of Oxidants in NF-{kappa}B Activation and TNF-{alpha} Gene Transcription Induced by Hypoxia and Endotoxin J. Immunol., July 15, 2000; 165(2): 1013 - 1021. [Abstract] [Full Text] [PDF]

				M. M. Ndengele, C. J. Bellone, A. J. Lechner, and G. M. Matuschak Brief hypoxia differentially regulates LPS-induced IL-1beta and TNF-alpha gene transcription in RAW 264.7 cells Am J Physiol Lung Cell Mol Physiol, June 1, 2000; 278(6): L1289 - L1296. [Abstract] [Full Text] [PDF]