Grimm M C, Elsbury S K, Pavli P, Doe W F
Division of Molecular Medicine, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
J Leukoc Biol. 1996 Jun;59(6):804-12. doi: 10.1002/jlb.59.6.804.
Peripheral blood monocytes are recruited to the inflamed mucosa of inflammatory bowel disease but the specific chemotactic signals responsible for their attraction are not known. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine with potent monocyte attracting and activating properties and the aim of this study was to examine its expression and production in inflammatory bowel disease. In situ hybridization demonstrated mRNA for MCP-1 in macrophages, some of which had been recently recruited from the circulation as demonstrated by their co-expression of the monocyte marker CD 14, as well as in smooth muscle and endothelial cells in inflamed mucosa. Immunohistochemical studies showed a corresponding distribution of MCP-1 protein production by macrophages, smooth muscle, and endothelial cells. By contrast minimal MCP-1 mRNA expression and protein were found in histologically normal mucosa. Macrophages isolated from surgically resected inflammatory bowel disease colons and examined by Northern analysis expressed MCP-1 mRNA significantly more frequently (15/24 vs. 0/19, P< 0.0001) than macrophages from histologically normal mucosa from colon cancer resections. Blood monocytes stimulated by lipopolysaccharide and treated with hydrocortisone, 5-aminosalicylic acid, or cyclosporin A showed reduced MCP-1 expression and production in the presence of these agents. This study demonstrates increased expression of MCP-1 mRNA and protein and cells of origin of MCP-1 in inflamed intestinal mucosa. Together with the demonstrated influence of therapeutic agents on monocyte MCP-1 production the findings suggest a role for MCP-1 in monocyte attraction to the mucosal lesion of inflammatory bowel disease.
外周血单核细胞被募集到炎症性肠病的炎症黏膜处，但负责吸引它们的特定趋化信号尚不清楚。单核细胞趋化蛋白-1（MCP-1）是一种具有强大单核细胞吸引和激活特性的趋化因子，本研究的目的是检测其在炎症性肠病中的表达和产生情况。原位杂交显示巨噬细胞中有MCP-1的mRNA，其中一些巨噬细胞是最近从循环中募集而来的，这可通过它们与单核细胞标志物CD 14的共表达得以证明，此外在炎症黏膜的平滑肌和内皮细胞中也有MCP-1的mRNA。免疫组织化学研究显示巨噬细胞、平滑肌和内皮细胞产生MCP-1蛋白的分布情况与之相对应。相比之下，在组织学正常的黏膜中发现MCP-1的mRNA表达和蛋白含量极少。通过Northern分析检测从手术切除的炎症性肠病结肠中分离出的巨噬细胞，发现其表达MCP-1 mRNA的频率显著高于从结肠癌切除术中获取的组织学正常黏膜中的巨噬细胞（15/24比0/19，P<0.0001）。用脂多糖刺激并用氢化可的松、5-氨基水杨酸或环孢素A处理的血液单核细胞在这些药物存在的情况下MCP-1的表达和产生减少。本研究表明炎症肠黏膜中MCP-1 mRNA和蛋白的表达增加以及MCP-1的细胞来源。连同所证明的治疗药物对单核细胞MCP-1产生的影响，这些发现提示MCP-1在单核细胞被吸引至炎症性肠病黏膜病变处发挥作用。
