DIRECT INVOLVEMENT OF MACROPHAGES IN DESTRUCTION OF BETA-CELLS LEADING TO DEVELOPMENT OF DIABETES IN VIRUS-INFECTED MICE
DIRECT INVOLVEMENT OF MACROPHAGES IN DESTRUCTION OF BETA-CELLS LEADING TO DEVELOPMENT OF DIABETES IN VIRUS-INFECTED MICE
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DOI：
10.2337/diabetes.40.12.1586
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发表时间：
1991-12-01
期刊：
影响因子：
7.7
通讯作者：
YOON, JW
中科院分区：
文献类型：
--
作者：
BAEK, HS;YOON, JW
在低剂量(1×10(2)个空斑形成单位/只)脑心肌炎(EMC-D)病毒感染前7天、2天和2天，单次注射完全弗氏佐剂(CFA)、1型卡拉胶(CAR)或二氧化硅，SJL/J小鼠的糖尿病发病率(100%)显著高于未经治疗的EMC-D病毒感染小鼠(40%)。从未感染的SJL/J小鼠中分离出巨噬细胞，并在低剂量EMC-D感染前2天转移到SJL/J小鼠体内。大约90%的小鼠患上了糖尿病，而只接受病毒治疗的小鼠中有30%患上了糖尿病。在单次注射CFA、CAR或二氧化硅后，通过联合使用抗Mac-1和抗Mac-2单抗来耗尽巨噬细胞，几乎完全防止了EMC-D病毒感染小鼠的β细胞破坏。此外，长期用二氧化硅治疗耗尽巨噬细胞的小鼠和病毒感染前用CAR治疗的10%的小鼠都没有患上糖尿病。在这些观察的基础上，我们得出结论，巨噬细胞直接参与了对β细胞的破坏，导致了EMC-D病毒感染小鼠的临床糖尿病的发展。
A single administration of complete Freund's adjuvant (CFA), type 1 carrageenan (Car), or silica 7, 2, and 2 days, respectively, before infection with a low dose (1 x 10(2) plaque-forming units/mouse) of encephalomyocarditis D (EMC-D) virus resulted in a significant increase in the incidence of diabetes in SJL/J mice (100%) compared with untreated EMC-D virus-infected mice (40%). Peritoneal macrophages were isolated from uninfected SJL/J mice, which had been treated once with silica, and transferred into SJL/J mice 2 days before low-dose EMC-D infection. Approximately 90% of the mice became diabetic, whereas 30% of mice that received virus alone became diabetic. The depletion of macrophages by treatment with the combined anti-Mac-1 and anti-Mac-2 monoclonal antibodies after a single administration of CFA, Car, or silica resulted in almost complete prevention of beta-cell destruction in EMC-D virus-infected mice. Furthermore, none of the mice in which macrophages were depleted by long-term treatment with silica and 10% of the mice treated with Car before virus infection became diabetic. On the basis of these observations, we conclude that macrophages are directly involved in the destruction of beta-cells, leading to the development of clinical diabetes in EMC-D virus-infected mice.