CELL-SPECIFIC EXPRESSION OF ALPHA(1)-ANTITRYPSIN IN HUMAN INTESTINAL EPITHELIUM
CELL-SPECIFIC EXPRESSION OF ALPHA(1)-ANTITRYPSIN IN HUMAN INTESTINAL EPITHELIUM
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DOI：
10.1172/jci116797
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发表时间：
1993-10-01
影响因子：
15.9
通讯作者：
RUBIN, DC
中科院分区：
文献类型：
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作者：
MOLMENTI, EP;PERLMUTTER, DH;RUBIN, DC
α 1-抗胰蛋白酶（α 1-AT）是一种主要来源于肝脏的急性期血浆蛋白，可抑制中性粒细胞弹性蛋白酶。以前的研究表明，α 1-AT也表达在人类肠上皮细胞中，因为α 1-AT mRNA可以通过RNA印迹分析在人类空肠中检测到，并且α 1-AT合成可以在人类肠腺癌细胞系Caco 2中检测到，其在组织培养中自发分化为绒毛样肠上皮细胞。为了明确地确定α 1-AT基因在体内人肠上皮细胞中的表达，我们通过原位杂交检测了人空肠和回肠的组织切片。结果表明，特异性杂交肠上皮细胞从基地， 绒毛的尖端。虽然没有杂交肠上皮细胞在大多数的隐窝，有强烈的特异性杂交在一个区域的隐窝。双标记免疫组织化学研究表明，α 1-AT和溶菌酶共定位于这个区域，表明它代表潘氏细胞。最后，有一个显着增加杂交α 1-AT mRNA在绒毛肠上皮细胞和潘氏细胞在克罗恩病。本研究的结果提供了明确的证据表明，α 1-AT在人体空肠和回肠肠上皮细胞在体内表达，并表明，α 1-AT也是潘氏细胞的产物。与其他研究的结果一起，这些数据提高了在用于诊断蛋白丢失性肠病的粪便α 1-AT清除试验中检测到的α 1-AT主要来自脱落的肠上皮细胞的可能性。
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.