The human alpha 1-antitrypsin gene is transcribed from two different promoters in macrophages and hepatocytes

In order to investigate the mechanism of expression of the human alpha 1-antitrypsin (alpha 1-AT) gene in macrophages, we have characterized the alpha 1-AT transcriptional units in these cells and discovered that there is a macrophage-specific promoter located approximately 2000 bp upstream of the hepatocyte-specific promoter. Transcription from the two alpha 1-AT promoters is mutually exclusive: the macrophage promoter is silent in hepatocytes and the hepatocyte promoter is silent in macrophages. In addition, in macrophages two distinct mRNAs are generated transcript by alternative splicing. These results suggest that alpha 1-AT gene transcription responds to two different cell-specific regulatory mechanisms.