Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden.
Histochem Cell Biol. 2009 Dec;132(6):599-612. doi: 10.1007/s00418-009-0647-4. Epub 2009 Oct 11.
The aim of this study was to investigate the cellular and molecular expression of tartrate resistant acid phosphatase (TRAP) as a marker of activated macrophages in macrophage dependent dextran sulphate sodium (DSS)-induced colitis in rats. In normal colon, TRAP+/CX(3)CR(1)+ macrophages were located in the upper part of the lamina propria. In the early stage (day 1-3) of acute colitis prior to histopathological changes, induction of the cytokines TNFalpha, IL-12 and IFN gamma occurred concomitant with increased mRNA and enzyme activity of TRAP along with a slight increase of TRAP immunolabelling in macrophages of the upper lamina propria, suggesting induction of TRAP in resident macrophages. Among these cytokines, TNFalpha up-regulated TRAP expression in the RAW 264.7 monocyte/macrophage cell line. In a later phase (day 7) with fulminant colitis, a massive infiltration of macrophages including recruited TRAP+/CCR2+ cells was observed also in the lower part of the lamina propria as well as in the submuscular layer. Additionally, differentiated cellular expression of pro- and mature TRAP also suggest that mucosal macrophages in the lower part of lamina propria bordering the sub-mucosa provide a source of replenishment of macrophages situated in the upper lamina propria. In conclusion, induction of TRAP provides an early sign of macrophage responsiveness in DSS induced colitis.
本研究旨在探讨抗酒石酸酸性磷酸酶(TRAP)作为在大鼠葡聚糖硫酸钠(DSS)诱导结肠炎中活化巨噬细胞标志物的细胞和分子表达。在正常结肠中,TRAP+/CX(3)CR(1)+巨噬细胞位于固有层的上部。在急性结肠炎的早期(第 1-3 天),在组织病理学改变之前,细胞因子 TNFalpha、IL-12 和 IFN gamma 的诱导伴随着 TRAP 的 mRNA 和酶活性的增加,以及固有层上部巨噬细胞中 TRAP 免疫标记的轻微增加,表明驻留巨噬细胞中 TRAP 的诱导。在这些细胞因子中,TNFalpha 上调了 RAW 264.7 单核/巨噬细胞系中 TRAP 的表达。在伴有暴发性结肠炎的后期(第 7 天),大量巨噬细胞浸润,包括募集的 TRAP+/CCR2+细胞,也存在于固有层的下部以及黏膜下层。此外,TRAP 的分化细胞表达也表明,固有层下部毗邻黏膜下层的黏膜巨噬细胞为位于固有层上部的巨噬细胞提供了补充来源。总之,TRAP 的诱导为 DSS 诱导结肠炎中巨噬细胞反应性提供了早期迹象。