Mei Q, Sundler F
Department of Physiology and Neuroscience, Lund University, Lund, Sweden.
Digestion. 1999;60(3):227-37. doi: 10.1159/000007663.
Although enterochromaffin-like (ECL) cells are the major source of histamine for the regulation of gastric acid secretion, their role in ulcer healing has not been fully investigated. The present study aimed to investigate changes in ECL cell components as well as markers for somatostatin cells, parietal cells and macrophages during the healing of experimental ulcers in rats.
Standardised ulcer was induced directly in the rat gastric mucosa by brief application of acetic acid. At different time intervals following ulcer induction (1-15 days), histamine, histidine decarboxylase (HDC), chromogranin A, pancreastatin, vesicular monoamine transporter 2 (VMAT-2), H-K-ATPase, somatostatin as well as ED1 and ED2 (macrophage markers) were localised by immunocytochemistry. ED1- and histamine-immunoreactive cells were counted at different time points. HDC- and VMAT-2-immunoreactive cells were demonstrated by double staining and counted. The mRNA of HDC, chromogranin A and somatostatin was demonstrated by in situ hybridisation and quantitated by computerised image analysis.
HDC immunoreactivity and mRNA were markedly reduced in the ECL cells at the ulcer margin from day 1 following ulcer induction and onwards; after day 5 HDC immunoreactivity and mRNA rose gradually and had almost normalised by day 15. This local and transient downregulation of HDC was accompanied by a similar decrease in ECL cell histamine. In contrast to HDC and histamine, other ECL cell components (chromogranin A, pancreastatin, VMAT-2) as well as somatostatin and H-K ATPase were still demonstrable at the ulcer margin and displayed no major changes at any time point studied. Of the macrophage markers, ED1, but not ED2, could be identified at the ulcer margin, and the number of ED1-immunoreactive cells was high in the ulcer margin from day 1 to day 5 after ulcer induction. The increase in ED1-positive cells and the decrease in HDC-expressing cells were coincident in time and localisation.
The present results revealed a local and transient downregulation of HDC in the ECL cells at the ulcer margin. This may account for the decrease in ECL cell histamine observed. The local infiltration of macrophages into the ulcer margin suggests that inflammatory mediators are involved in the local suppression of ECL cell activity during ulcer healing.
尽管肠嗜铬样（ECL）细胞是调节胃酸分泌的组胺的主要来源，但其在溃疡愈合中的作用尚未得到充分研究。本研究旨在探讨大鼠实验性溃疡愈合过程中ECL细胞成分以及生长抑素细胞、壁细胞和巨噬细胞标志物的变化。
通过短暂应用乙酸直接在大鼠胃黏膜诱导标准化溃疡。在溃疡诱导后的不同时间间隔（1 - 15天），通过免疫细胞化学定位组胺、组氨酸脱羧酶（HDC）、嗜铬粒蛋白A、胰抑制素、囊泡单胺转运体2（VMAT - 2）、H - K - ATP酶、生长抑素以及ED1和ED2（巨噬细胞标志物）。在不同时间点对ED1和组胺免疫反应性细胞进行计数。通过双重染色显示并计数HDC和VMAT - 2免疫反应性细胞。通过原位杂交显示HDC、嗜铬粒蛋白A和生长抑素的mRNA，并通过计算机图像分析进行定量。
从溃疡诱导后第1天起，溃疡边缘ECL细胞中的HDC免疫反应性和mRNA显著降低；第5天后，HDC免疫反应性和mRNA逐渐升高，到第15天几乎恢复正常。HDC的这种局部和短暂下调伴随着ECL细胞组胺的类似减少。与HDC和组胺不同，其他ECL细胞成分（嗜铬粒蛋白A、胰抑制素、VMAT - 2）以及生长抑素和H - K ATP酶在溃疡边缘仍可检测到，并且在研究的任何时间点均未显示出重大变化。在巨噬细胞标志物中，在溃疡边缘可识别出ED1而非ED2，并且在溃疡诱导后第1天至第5天，溃疡边缘ED1免疫反应性细胞数量较高。ED1阳性细胞的增加和HDC表达细胞的减少在时间和定位上是一致的。
本研究结果揭示了溃疡边缘ECL细胞中HDC的局部和短暂下调。这可能解释了观察到的ECL细胞组胺的减少。巨噬细胞向溃疡边缘的局部浸润表明炎症介质参与了溃疡愈合过程中ECL细胞活性的局部抑制。
