Williams E J, Haque S, Banks C, Johnson P, Sarsfield P, Sheron N
Department of Cell and Molecular Medicine, D Level, South Academic Block, Southampton General Hospital, Southampton, SO16 6YD, UK.
J Pathol. 2000 Dec;192(4):533-9. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH732>3.0.CO;2-X.
There is increasing evidence to suggest that the potent neutrophil chemoattractant interleukin-8 (IL-8) has an important role in the pathogenesis of inflammatory bowel disease. IL-8 mediates its actions via two cell surface receptors, CXCR1 and CXCR2. This paper describes the distribution of these IL-8 receptors in the normal gastrointestinal tract and how this is modified in ulcerative colitis (UC). Paraffin-embedded colonic resection specimens were stained with monoclonal antibodies directed against CXCR1 and CXCR2 in ten cases of total UC, 16 cases of appendicitis, and 11 histologically normal sections. A semiquantitative scale of 0-4 was used to assess the proportion and intensity of positively stained cells within certain defined areas of tissue. A comparative assessment was made of the distribution of various cell populations. Dual immunostaining was used to confirm the phenotype of positively staining cells. In the histologically normal colon, the antibody against CXCR1 stained a subpopulation of macrophages deep to the epithelium and germinal centre lymphocytes. A similar pattern of staining was seen in acute appendicitis, with in addition some positively stained neutrophil polymorphs. In UC, there was up-regulation of CXCR1, with a striking increase in positively stained macrophages throughout the mucosa and of B and T lymphocytes outside the germinal centre areas. There was also intense up-regulation of CXCR1 expression by the luminal epithelium, reflected in the epithelial staining score (mean+/-SE=1.8+/-0.44 for UC cases, vs. 0.23+/-0.16 for controls and 0.25+/-0.14 for acute appendicitis). CXCR2 was only expressed on a small population of lamina propria mononuclear cells and crypt epithelial cells, with no significant differences observed between the groups. These results suggest that IL-8 may, through CXCR1, have a role beyond neutrophil recruitment in mediating the immune response in UC and that this is not merely a consequence of the acute inflammation seen in UC.
越来越多的证据表明，强效中性粒细胞趋化因子白细胞介素 - 8（IL - 8）在炎症性肠病的发病机制中起重要作用。IL - 8通过两种细胞表面受体CXCR1和CXCR2介导其作用。本文描述了这些IL - 8受体在正常胃肠道中的分布以及在溃疡性结肠炎（UC）中是如何改变的。对10例全结肠炎、16例阑尾炎及11例组织学正常切片的石蜡包埋结肠切除标本，用针对CXCR1和CXCR2的单克隆抗体进行染色。采用0 - 4的半定量评分标准评估组织特定区域内阳性染色细胞的比例和强度。对不同细胞群体的分布进行了比较评估。采用双重免疫染色来确认阳性染色细胞的表型。在组织学正常的结肠中，抗CXCR1抗体染色上皮深层的巨噬细胞亚群和生发中心淋巴细胞。在急性阑尾炎中也观察到类似的染色模式，此外还有一些阳性染色的中性多形核白细胞。在UC中，CXCR1上调，整个黏膜中阳性染色的巨噬细胞以及生发中心区域外的B和T淋巴细胞显著增加。管腔上皮细胞的CXCR1表达也强烈上调，这反映在上皮染色评分上（UC病例的平均±标准误=1.8±0.44，对照组为0.23±0.16，急性阑尾炎为0.25±0.14）。CXCR2仅在一小部分固有层单核细胞和隐窝上皮细胞上表达，各组之间未观察到显著差异。这些结果表明，IL - 8可能通过CXCR1在介导UC免疫反应中发挥超出中性粒细胞募集的作用，且这不仅仅是UC中急性炎症的结果。
