Prostanoids in human colonic mucosa:: Effects of inflammation on PGE2 receptor expression
Prostanoids in human colonic mucosa:: Effects of inflammation on PGE2 receptor expression
复制标题
DOI：
10.1016/s0198-8859(00)00131-2
复制
发表时间：
2000-07-01
期刊：
影响因子：
2.7
通讯作者：
Roche, JK
中科院分区：
文献类型：
--
作者：
Cosme, R;Lublin, D;Roche, JK
虽然在粘膜炎症过程中PGE（2）的组织浓度升高3倍或更多，但前列腺素类在人类粘膜中的细胞靶点以及由此引起的细胞生理学变化尚未得到充分研究。我们使用一组免疫球蛋白和mRNA探针，以定位和定量前列腺素受体EP家族的四个成员结合PGE（2）的组织学正常和发炎的人结肠粘膜细胞，然后检查前列腺素诱导的粘膜淋巴细胞功能的变化。前列腺素受体选择性地表达在有限数量的人结肠粘膜细胞上; EP 4单独表达在固有层单核细胞上。双重原位免疫染色证实，正常粘膜中CD 3（+）T淋巴细胞是主要的EP 4受体携带细胞。流式细胞仪检测结果显示，19.2%的固有层单个核细胞为EP 4+，其中近30%为CD 3+。地高辛标记的RNA探针原位杂交在很大程度上证实了这一定位。在炎症过程中，粘膜T淋巴细胞表现出显着增强的EP 4免疫反应性受体蛋白。单细胞的计算机辅助密度测定显示荧光强度从4.8 +/- 1.8增加到8.6 +/- 1.8（p < 0.04）。PGE（2）的作用包括使T淋巴细胞IL-2分泌减少35%。考克斯1（+）固有层细胞在炎症过程中数量几乎翻倍;表达T淋巴细胞标记物;但每个细胞的免疫反应性考克斯1蛋白量保持不变。新出现的考克斯2（+）淋巴细胞数量仍有保留
Although the tissue concentration of PGE(2) is heightened 3-fold or more during mucosal inflammation the cellular targets of prostanoids in human mucosa and the resulting changes in cell physiology have not been fully explored. We used a panel of immunoglobulin and mRNA probes in order to localize and quantitate che four member EP family of prostanoid receptors for binding PGE(2) to cells of histologically normal and inflamed human colonic mucose, and then examined prostanoid-induced changes in mucosal lymphocyte function. Prostanoid receptors were selectively expressed on a limited number of human colonic mucosal cells; EP4 alone was expressed on lamina propria mononuclear cells. Dual immunostaining in situ identified the CD3(+) T lymphocyte as a major EP4 receptor-bearing cell in normal mucosa. Flow cytometry of isolated cells showed that 19.2% of lamina propria mononuclear cells were EP4+, and almost 30% of these were CD3(+). In situ hybridization with digoxygenin-labeled RNA probes largely confirmed this localization. During inflammation, mucosal T lymphocytes showed a significant enhancement in EP4 immunoreactive receptor protein. Computer-assisted densitometry of single cells demonstrated an increase in fluorescence intensity from 4.8 +/- 1.8 to 8.6 +/- 1.8 (p < 0.04). The effects of PGE(2) included a 35% reduction in T lymphocyte IL-2 secretion. COX 1(+) lamina propria cells nearly doubled in number during inflammation; expressed a T lymphocyte marker; but retained an unchanged quantity of immunoreactive COX 1 protein per cell. The number of newly appeared COX 2(+) lymphocytes remained