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

Alpha1-Antitrypsin (alpha1-AT) is an acute phase plasma protein predom inantly derived from the liver which inhibits neutrophil elastase. Pre vious 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 d ifferentiates into villous-like enterocytes in tissue culture. To defi nitively determine that the alpha1-AT gene is expressed in human enter ocytes in vivo, we examined tissue slices of human jejunum and ileum b y in situ hybridization. The results demonstrate specific hybridizatio n to enterocytes from the bases to the tips of the villi. Although the re 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 ly sozyme co-localized to this region, indicating that it represented Pan eth cells. Finally, there was a marked increase in hybridization to al pha1-AT mRNA in villous enterocytes and Paneth cells in Crohn's diseas e. The results of this study provide definitive evidence that alpha1-A T is expressed in human jejunal and ileal enterocytes in vivo, and sho w 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 protei n-losing enteropathies is predominantly derived from sloughed enterocy tes.