Josefsen K, Nielsen H, Lorentzen S, Damsbo P, Buschard K
Bartholin Instituttet, Kommunehospitalet, Copenhagen K, Denmark.
Clin Exp Immunol. 1994 Dec;98(3):489-93. doi: 10.1111/j.1365-2249.1994.tb05517.x.
Investigations in the BB rat and the non-obese diabetic (NOD) mouse have provided substantial evidence for the involvement of the monocyte/macrophage system in the development of type 1 diabetes mellitus. However, it is not known whether monocytes play the same role in the pathogenesis of human type 1 diabetes. We investigated this problem in a longitudinal study of 29 recent-onset type 1 diabetes mellitus patients. Monocyte chemotaxis, phagocytosis and superoxide production as well as metabolic and haematological parameters were studied immediately after diagnosis and 6 months later. At diagnosis the patients had activated casein and C5a chemotaxis (casein 70 +/- 9 versus 150 +/- 5 (mean +/- s.e.m.), P < 0.001; C5a 137 +/- 10 versus 158 +/- 5, P < 0.05 (activation immobilizes monocytes, reducing the measured values)), and activated superoxide production (3.6 +/- 0.3 versus 3.0 +/- 0.3, P < 0.05). After 6 months casein chemotaxis (115 +/- 16 versus 150 +/- 5, P < 0.05) and Candida phagocytosis (3.3 +/- 0.1 versus 2.8 +/- 0.2, P < 0.001) were still activated. There was no correlation with other clinical or paraclinical parameters. We conclude that the circulating monocytes in newly diagnosed type 1 diabetes patients are activated. It is reasonable to expect that monocytes at the local site of inflammation in pancreas are even further activated. This could play a pathogenic role in beta cell destruction.
对BB大鼠和非肥胖糖尿病(NOD)小鼠的研究为单核细胞/巨噬细胞系统参与1型糖尿病的发生发展提供了大量证据。然而,尚不清楚单核细胞在人类1型糖尿病发病机制中是否发挥相同作用。我们对29例新诊断的1型糖尿病患者进行了一项纵向研究,以探讨这一问题。在诊断后及6个月后,研究了单核细胞趋化性、吞噬作用、超氧化物生成以及代谢和血液学参数。诊断时,患者的酪蛋白和C5a趋化性被激活(酪蛋白:70±9对150±5(平均值±标准误),P<0.001;C5a:137±10对158±5,P<0.05(趋化性激活会使单核细胞固定,从而降低测量值)),超氧化物生成也被激活(3.6±0.3对3.0±0.3,P<0.05)。6个月后,酪蛋白趋化性(115±16对150±5,P<0.05)和白色念珠菌吞噬作用(3.3±0.1对2.8±0.2,P<0.001)仍处于激活状态。与其他临床或临床旁参数无相关性。我们得出结论,新诊断的1型糖尿病患者的循环单核细胞被激活。可以合理推测,胰腺炎症局部部位的单核细胞会被进一步激活。这可能在β细胞破坏中发挥致病作用。