Macrophages infiltrating the tissue in chronic pancreatitis express the chemokine receptor CCR5
Macrophages infiltrating the tissue in chronic pancreatitis express the chemokine receptor CCR5
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DOI：
10.1067/msy.2000.108613
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发表时间：
2000-11-01
期刊：
影响因子：
3.8
通讯作者：
Büchler, MW
中科院分区：
文献类型：
--
作者：
Goecke, H;Forssmann, U;Büchler, MW
背景：慢性胰腺炎（CP）发生的免疫学机制尚不清楚。慢性炎症组织含有表达CC趋化因子受体5 （CCR5）的单核细胞数量增加，CCR5也是嗜巨噬细胞毒株进入HIV的辅助受体。然而，该受体是否参与CP的炎症过程尚不清楚。在本研究中，我们分析了CCR5在CP中的表达，在炎症细胞上检测到趋化因子受体可能强烈提示它们参与了CP的发病机制（即吸引和激活这些细胞）。为了进一步验证这一点，我们连续分析了CCR5的两个配体：RANTES和MIP-1 α的表达。对22例CP患者和7例健康胰腺的胰腺组织样本进行了评价。采用Northern blot分析CCR5、RANTES和MIP-1 α。连续组织切片染色CCR5， CD3和CD68，以确定在CT中表达CCR5的白细胞亚型！结果。通过Northern blot分析，CP标本的CCR5、RANTES和MIP-1 α信使RNA （mRNA）水平分别比健康对照组高12.9倍、13.3倍和9.2倍（P < 0.01）。CCR5免疫染色显示，与健康胰腺相比，CP组织中CCR5阳性细胞增加了30倍。连续组织切片染色显示，大部分ccr5阳性细胞同时也是cd68阳性细胞（巨噬细胞）。我们的数据表明，CP中CCR5阳性细胞中有相当一部分是巨噬细胞。CCR5很可能参与了这些巨噬细胞的吸引和激活，因为CCR5配体RANTES和MIP-1同时上调。
Background, The immunologic mechanisms involved in the development of chronic pancreatitis (CP) are poorly understood. Chronically inflamed tissues contain increased numbers of mononuclear cells expressing the CC chemokine receptor 5 (CCR5), which is also a coreceptor for HIV entry of macrophage tropic strains. However, whether this receptor is involved in the inflammatory process in CP is not known. In the current study we analyzed the expression of CCR5 in CP. The detection of chemokine receptors on inflammatory cells would strongly suggest their involvement in the pathogenesis of CP (ie, attraction and activation of these cells). To further evaluate this, we consecutively analyzed the expression of 2 ligands of CCR5: RANTES and MIP-1 alpha.Methods. Pancreatic tissue samples of 22 patients with CP and of 7 healthy pancreas were evaluated. CCR5, RANTES, and MIP-1 alpha were analyzed by Northern blot analysis. Consecutive tissue sections were stained for CCR5, CD3, and CD68 to define the leukocyte subtype expressing CCR5 in CT!Results. By Northern blot analysis, CCR5, RANTES, and MIP-1 alpha messenger RNA (mRNA) levels were 12.9-fold 13.3-fold and 9.2-fold higher in CP specimens compared with healthy controls, respectively (P < .01). Immunostaining for CCR5 revealed a 30-fold increase of CCR5-positive cells in CP tissue compared with the healthy pancreas. Staining of consecutive tissue sections revealed that the majority of CCR5-positive cells were also CD68-positive (macrophages).Conclusions. Our data indicate that a remarkable portion of CCR5 positive cells in CP are macrophages. CCR5 is most likely involved in the attraction and activation of these macrophages, since the CCR5 ligands RANTES and MIP-1 are concomitantly upregulated.