CERULOPLASMIN GENE-EXPRESSION IN SILICOTIC RAT LUNG

Objective To investigate whether the silicotic process leads to the pr edominant extrahepatic ceruloplasmin (Cp) gene expression found within the plasma and lung tissue contributing to the significant increase. Methods The previous work of our research group demonstrated changes o f ceruloplasmin (Cp) in rat lung tissue and alveolar macrophages durin g silicosis by electrophoresis analysis, radioimmunological assay and immunoflurescent technique. It is of interest to clarify the cause of elevation of Cp, particularly in the silicotic lung. Though Cp is main ly synthesized in the liver, recent studies have also demonstrated Cp synthesis in rat sertoli cells and human synovial tissue. Wistar male rats (180-220 g) were instilled intratracheally with 50 mg of silica ( more than 97% of SiO2 and 95% of the silica particles with diameters l ess than 5 mu m) suspended in 1.0 ml saline. Rats were killed for exci sing their lung and liver on the 21st day after instillation. Lung cel ls were harvested by repeated bronchial lavages with saline. Monolayer cells were cultured for 12-16 hours in the serum-free culture medium. Then the alveolar macrophages were collected for assay. Results Dot b lotting results showed that Cp mRNA content increased in the liver as expected and was also detectable in the lung, with a nearly 2-fold inc rease compared with the normal rat lung in the normal group (saline in jection). In situ hybrodization and Northern blotting revealed that th e lung mesenchymal cells and the alveolar macrophages can express Cp m RNA in silicosis. Conclusions These data indicate that the lung is a p rominent site of extrahepatic Cp gene expression during silicosis, thu s suggesting that this protein may play a previously unknown role in p ulmonary injury or repair.