Cell type-specific and inflammatory-induced expression of haptoglobin gene in lung

BACKGROUND: Haptoglobin (HP) is a hemoglobin-binding protein and a major acute phase reactant. Recently, HP has been shown to possess antioxidant and angiogenic properties. HP is known to be produced mainly in the liver. Expression of HP in specific cells of nonhepatic origin including lung cells has not been studied before. The presence of extracellular plasma proteins in lung epithelial fluid has been assumed to be of blood serum origin. EXPERIMENTAL DESIGN: To investigate the expression of the HP gene in lung, the presence of HP mRNA and the production of HP protein in the lung were examined by Northern blot analysis and immunoprecipitation, respectively. Cellular expression of HP during development and inflammation were studied by in situ hybridization with lung tissues derived from different gestational stages from baboons and mice and from mice treated with lipopolysaccharide. RESULTS: Northern blot and in situ hybridization analyses established a high level of expression of HP in fetal and adult lung tissues, which were confined to the epithelial lining of the airways in mouse and baboon. After inflammation had been induced in vivo, expression of the HP gene rose fourfold in lung, an increase compatible with that observed in normal mouse liver. However, HP mRNA level was not significantly altered in airway epithelium. Instead, HP expression in alveolar epithelial cells, most likely type 2 cells, was strongly increased. CONCLUSIONS: Our data suggest that locally synthesized HP provides a major source of antioxidant and/or antimicrobial activity in the mucus blanket as well as in the alveolar fluid in the lung. The regulation and cell type-specific expression of HP during development and inflammation indicate a protective role for HP in lung and confirm recent reports that HP plays important roles in protecting against infection and in repairing injured tissues.