Gassler Nikolaus, Schnölzer Martina, Rohr Claudia, Helmke Burkhard, Kartenbeck Jürgen, Grünewald Sylvia, Laage Rico, Schneider Armin, Kränzlin Bettina, Bach Alfred, Otto Herwart F, Autschbach Frank
Department of Pathology, Heidelberg University, Mannheim, Germany.
Lab Invest. 2002 Dec;82(12):1647-59. doi: 10.1097/01.lab.0000041709.42598.4a.
It has been suggested that the behavior and function of Paneth cells in metaplasia are different from those found in normal intestinal mucosa. In this study, we investigated whether calnexin, a protein involved in secretory pathways, might be associated with differentiation and function of Paneth cells in normal small intestine, in complete intestinal metaplasia of the stomach, and in Paneth cell-rich adenomas. Differentiation and function of Paneth cells was monitored by Ki67, lysozyme, and morphologic features. Using a newly established monoclonal antibody, we found that calnexin is regularly synthesized by Paneth cells of normal small intestine. In these cells, the staining intensity of calnexin was inversely correlated with their content of secretory granules (lysozyme). In contrast, Paneth cells of intestinal metaplasia and Paneth cell-rich adenomas showed a reduced immunostaining of both calnexin and lysozyme. Moreover, these Paneth cells synthesized the proliferation marker Ki67, a phenomenon that was never observed in Paneth cells of normal small intestine. In vitro experiments using CaCo2 cells showed that the expression of calnexin is not directly affected by the induction of mitosis. In conclusion, calnexin probably reflects the status of Paneth cell differentiation and function. The results do not necessarily indicate that calnexin has a function in Paneth cell proliferation.
有人提出，化生过程中潘氏细胞的行为和功能与正常肠黏膜中的不同。在本研究中，我们调查了参与分泌途径的钙连接蛋白是否可能与正常小肠、胃完全肠化生以及富含潘氏细胞的腺瘤中潘氏细胞的分化和功能有关。通过Ki67、溶菌酶和形态学特征监测潘氏细胞的分化和功能。使用新建立的单克隆抗体，我们发现正常小肠的潘氏细胞能正常合成钙连接蛋白。在这些细胞中，钙连接蛋白的染色强度与其分泌颗粒（溶菌酶）的含量呈负相关。相比之下，肠化生的潘氏细胞和富含潘氏细胞的腺瘤中钙连接蛋白和溶菌酶的免疫染色均降低。此外，这些潘氏细胞合成增殖标志物Ki67，而在正常小肠的潘氏细胞中从未观察到这种现象。使用CaCo2细胞进行的体外实验表明，钙连接蛋白的表达不受有丝分裂诱导的直接影响。总之，钙连接蛋白可能反映了潘氏细胞的分化和功能状态。结果不一定表明钙连接蛋白在潘氏细胞增殖中起作用。
