Cell-specific expression of alpha 1-antitrypsin in human intestinal epithelium.
AUTOR(ES)
Molmenti, E P
RESUMO
alpha 1-Antitrypsin (alpha 1-AT) is an acute phase plasma protein predominantly derived from the liver which inhibits neutrophil elastase. Previous studies have suggested that alpha 1-AT is also expressed in human enterocytes because alpha 1-AT mRNA could be detected in human jejunum by RNA blot analysis, and alpha 1-AT synthesis could be detected in a human intestinal adenocarcinoma cell line Caco2, which spontaneously differentiates into villous-like enterocytes in tissue culture. To definitively determine that the alpha 1-AT gene is expressed in human enterocytes in vivo, we examined tissue slices of human jejunum and ileum by in situ hybridization. The results demonstrate specific hybridization to enterocytes from the bases to the tips of the villi. Although there was no hybridization to enterocytes in most of the crypt epithelium, there was intense specific hybridization in one region of the crypt. Double-label immunohistochemical studies showed that alpha 1-AT and lysozyme co-localized to this region, indicating that it represented Paneth cells. Finally, there was a marked increase in hybridization to alpha 1-AT mRNA in villous enterocytes and Paneth cells in Crohn's disease. The results of this study provide definitive evidence that alpha 1-AT is expressed in human jejunal and ileal enterocytes in vivo, and show that alpha 1-AT is also a product of Paneth cells. Together with the results of other studies, these data raise the possibility that alpha 1-AT detected in fecal alpha 1-AT clearance assays for diagnosing protein-losing enteropathies is predominantly derived from sloughed enterocytes.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=288370Documentos Relacionados
- Cis- and trans-acting elements responsible for the cell-specific expression of the human alpha 1-antitrypsin gene.
- A cell-specific enhancer of the mouse alpha 1-antitrypsin gene has multiple functional regions and corresponding protein-binding sites.
- Stable expression and cell-specific chromatin structure of human α1-antitrypsin cosmid transgenes in rat hepatoma cells
- Cell-specific expression of a Clara cell secretory protein-human growth hormone gene in the bronchiolar epithelium of transgenic mice.
- Alpha 1-antitrypsin deficiency caused by the alpha 1-antitrypsin Nullmattawa gene. An insertion mutation rendering the alpha 1-antitrypsin gene incapable of producing alpha 1-antitrypsin.