CELL-TYPE-SPECIFIC AND INFLAMMATORY-INDUCED EXPRESSION OF HAPTOGLOBINGENE IN LUNG

BACKGROUND: Haptoglobin (DR) is a hemoglobin-binding protein and a maj or acute phase reactant. Recently, HP has been shown to possess antiox idant and angiogenic properties. HP is known to be produced mainly in the liver. Expression of HP in specific cells of nonhepatic origin inc luding lung cells has not been studied before. The presence of extrace llular plasma proteins in lung epithelial fluid has been assumed to be of blood serum origin. EXPERIMENTAL DESIGN: To investigate the expres sion of the HP gene in lung, the presence of HP mRNA and the productio n of HP protein in the lung were examined by Northern blot analysis an d immunoprecipitation, respectively. Cellular expression of HP during development and inflammation were studied by in situ hybridization wit h lung tissues derived from different gestational stages from baboons and mice and from mice treated with lipopolysaccharide. RESULTS: North ern blot and in situ hybridization analyses established a high level o f expression of HP in fetal and adult lung tissues, which were confine d to the epithelial lining of the airways in mouse and baboon. After i nflammation had been induced in vivo, expression of the HP gene rose f ourfold in lung, an increase compatible with that observed in normal m ouse liver. However, HP mRNA level was not significantly altered in ai rway epithelium. Instead, HP expression in alveolar epithelial cells, most likely type 2 cells, was strongly increased. CONCLUSIONS: Our dat a suggest that locally synthesized HP provides a major source of antio xidant and/or antimicrobial activity in the mucus blanket as well as i n the alveolar fluid in the lung. The regulation and cell type-specifi c expression of HP during development and inflammation indicate a prot ective role for HP in lung and confirm recent reports that HP plays im portant roles in protecting against infection and in repairing injured tissues.