CELL-SPECIFIC EXPRESSION OF ALPHA(1)-ANTITRYPSIN IN HUMAN INTESTINAL EPITHELIUM

Alpha1-Antitrypsin (alpha1-AT) is an acute phase plasma protein predominantly derived from the liver which inhibits neutrophil elastase. Previous studies have suggested that alpha1-AT is also expressed in human enterocytes because alpha1-AT mRNA could be detected in human jejunum by RNA blot analysis, and alpha1-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 alpha1-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 alpha1-AT and lysozyme co-localized to this region, indicating that it represented Paneth cells. Finally, there was a marked increase in hybridization to alpha1-AT mRNA in villous enterocytes and Paneth cells in Crohn's disease. The results of this study provide definitive evidence that alpha1-AT is expressed in human jejunal and ileal enterocytes in vivo, and show that alpha1-AT is also a product of Paneth cells. Together with the results of other studies, these data raise the possibility that alpha1-AT detected in fecal alpha1-AT clearance assays for diagnosing protein-losing enteropathies is predominantly derived from sloughed enterocytes.