Acute hypoxia increases alveolar macrophage tumor necrosis factor activity and alters NF-kappa B expression

• Published in: American journal of physiology. Lung cellular and molecular physiology 1999-06, Vol.276 (6), p.909-L916
• Main Authors: Leeper-Woodford, Sandra K, Detmer, Kristina
• Format: Article
• Language: English
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.1999.276.6.l909

Departments of 1  Physiology and 2  Biochemistry, Mercer University School of Medicine, Macon, Georgia 31207 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 O 2 tension. It is thus proposed that acute changes in O 2 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 (10 6 /ml) were incubated (37°C at 5% CO 2 ) for 2 h with LPS ( Pseudomonas aeruginosa , 1 µg/ml) in normoxia (21% O 2 -5% CO 2 ) or hypoxia (1.8% O 2 -5% CO 2 ). 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