Bai Yan, Robinson Elizabeth, Chai Ryan, Ross Jacqueline M, Reddy Shiva
School of Biological Sciences, University of Auckland, Private Bag, 92019, Auckland, New Zealand.
J Mol Histol. 2006 May;37(3-4):101-13. doi: 10.1007/s10735-006-9045-6. Epub 2006 Jul 29.
In type 1 diabetes mellitus (T1DM), the processes which control the recruitment of immune cells into pancreatic islets are poorly defined. Complex interactions involving adhesion molecules, chemokines and chemokine receptors may facilitate this process. The chemokine, monocyte chemoattractant protein-1 (MCP-1), previously shown to be important in leukocyte trafficking in other disease systems, may be a key participant in the early influx of blood-borne immune cells into islets during T1DM. In the non-obese diabetic (NOD) mouse, the expression of MCP-1 protein has not been demonstrated. We employed dual-label immunohistochemistry to examine the intra-islet expression, distribution and cellular source of MCP-1 in the NOD mouse following cyclophosphamide administration. NOD mice were treated with cyclophosphamide at day 72-73 and MCP-1 expression studied at days 0, 4, 7, 11 and 14 after treatment and comparisons were made between age-matched NOD mice treated with diluent and non-diabetes-prone CD-1 mice. Pancreatic expression of MCP-1 was also examined in NOD mice at various stages of spontaneous diabetes. In the cyclophosphamide group at day 0, MCP-1 immunolabelling was present in selective peri-islet macrophages but declined at day 4. It increased slightly at day 7 but was more marked from day 11, irrespective of diabetes development. The pattern of MCP-1 expression in macrophages was different over time in both the cyclophosphamide and control groups. In the cyclophosphamide group, there was a change over time with an increase at day 11. In the control group, there was little evidence of change over time. There was no significant difference in the mean percentage of MCP-1 positive macrophages between the cyclophosphamide-treated diabetic and non-diabetic mice. During spontaneous diabetes in the NOD mouse, only a few peri-islet MCP-1 cells appeared at day 45. These became more numerous from day 65 but were absent at diabetes onset. We speculate that a proportion of early islet-infiltrating macrophages which express MCP-1 may attract additional lymphocytes and macrophages into the early inflamed islets and intensify the process of insulitis.
在1型糖尿病（T1DM）中，控制免疫细胞向胰岛募集的过程尚不清楚。涉及黏附分子、趋化因子和趋化因子受体的复杂相互作用可能促进这一过程。趋化因子单核细胞趋化蛋白-1（MCP-1）先前已证实在其他疾病系统的白细胞运输中起重要作用，它可能是T1DM期间血源免疫细胞早期流入胰岛的关键参与者。在非肥胖糖尿病（NOD）小鼠中，尚未证实MCP-1蛋白的表达。我们采用双标记免疫组织化学法，检测环磷酰胺给药后NOD小鼠胰岛内MCP-1的表达、分布及细胞来源。在第72 - 73天给NOD小鼠注射环磷酰胺，并在治疗后的第0、4、7、11和14天研究MCP-1的表达，同时与用稀释剂处理的年龄匹配的NOD小鼠和不易患糖尿病的CD-1小鼠进行比较。还在NOD小鼠自发性糖尿病的不同阶段检测了胰腺中MCP-1的表达。在环磷酰胺组第0天，MCP-1免疫标记出现在选择性胰岛周围巨噬细胞中，但在第4天下降。在第7天略有增加，但从第11天起更明显，与糖尿病的发展无关。环磷酰胺组和对照组巨噬细胞中MCP-1表达模式随时间不同。在环磷酰胺组，随时间有变化，在第11天增加。在对照组，几乎没有随时间变化的证据。环磷酰胺治疗的糖尿病小鼠和非糖尿病小鼠之间，MCP-1阳性巨噬细胞的平均百分比没有显著差异。在NOD小鼠自发性糖尿病期间，在第45天仅出现少数胰岛周围MCP-1细胞。从第65天起这些细胞增多，但在糖尿病发病时消失。我们推测，一部分表达MCP-1的早期胰岛浸润巨噬细胞可能吸引更多淋巴细胞和巨噬细胞进入早期炎症胰岛，并加剧胰岛炎过程。
