The role of MAC1 in diesel exhaust particle-induced microglial activation and loss of dopaminergic neuron function.
The role of MAC1 in diesel exhaust particle-induced microglial activation and loss of dopaminergic neuron function.
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DOI：
10.1111/jnc.12231
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发表时间：
2013-06
影响因子：
4.7
通讯作者：
Block ML
中科院分区：
文献类型：
--
作者：
Levesque S;Taetzsch T;Lull ME;Johnson JA;McGraw C;Block ML
越来越多的报告支持空气污染导致神经炎症，并与中枢神经系统（CNS）疾病/损伤有关。柴油机尾气颗粒物（DEP）是城市空气污染的主要组成部分，它与小胶质细胞活化和帕金森病样病理学有关。为了开始阐明DEP如何发挥CNS作用，用纳米尺寸的DEP（<0.22 μM; 50μg/mL）、超细炭黑（ufCB，50 μ g/ml）或DEP提取物（eDEP;来自50 μg/ml DEP）处理小胶质细胞和神经元-胶质细胞培养物，并评估小胶质细胞活化和多巴胺能（DA）神经元功能的作用。所有这三种治疗均表现出增强的变形小胶质细胞形态，增加H2 O2的产生，并减少DA的摄取。机制研究表明，清道夫受体抑制剂岩藻依聚糖阻断DEP在小胶质细胞的内化，但未能改变DEP诱导的H2 O2在小胶质细胞的生产。然而，预处理与MAC 1/CD 11b抑制剂抗体阻断小胶质细胞H2 O2的生产响应DEP。MAC 1 −/−中脑神经元-胶质细胞培养物受到保护，不受DEP诱导的DA神经元功能丧失的影响，这通过DA摄取来测量。这些发现支持DEP可能通过多种机制激活小胶质细胞，其中清道夫受体调节DEP的内化，而MAC 1受体对于DEP诱导的小胶质细胞H2 O2产生和DA神经元功能丧失都是必需的。
Increasing reports support that air pollution causes neuroinflammation and is linked to central nervous system (CNS) disease/damage. Diesel exhaust particles (DEP) are a major component of urban air pollution, which has been linked to microglial activation and Parkinson’s disease-like pathology. To begin to address how DEP may exert CNS effects, microglia and neuron-glia cultures were treated with either nanometer-sized DEP (<0.22 µM; 50µg/mL), ultrafine carbon black (ufCB, 50µg/ml), or DEP extracts (eDEP; from 50 µg/ml DEP) and the effect of microglial activation and dopaminergic (DA) neuron function was assessed. All three treatments showed enhanced amoeboid microglia morphology, increased H2O2 production, and decreased DA uptake. Mechanistic inquiry revealed that the scavenger receptor inhibitor fucoidan blocked DEP internalization in microglia, but failed to alter DEP-induced H2O2 production in microglia. However, pretreatment with the MAC1/CD11b inhibitor antibody blocked microglial H2O2 production in response to DEP. MAC1−/− mesencephalic neuron-glia cultures were protected from DEP-induced loss of DA neuron function, as measured by DA uptake. These findings support that DEP may activate microglia through multiple mechanisms, where scavenger receptors regulate internalization of DEP and the MAC1 receptor is mandatory for both DEP-induced microglial H2O2 production and loss of DA neuron function.
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影响因子：
5
作者：
Cordier, S;Monfort, C;Arslan, A
通讯作者：
Arslan, A
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影响因子：
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