Atypical anti inflammatory activation of microglia induced by apoptotic neurons - Possible role of phosphatidylserine-phosphatidylserine receptor interaction
Atypical anti inflammatory activation of microglia induced by apoptotic neurons - Possible role of phosphatidylserine-phosphatidylserine receptor interaction
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DOI：
10.1385/mn:29:2:197
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发表时间：
2004-04-01
影响因子：
5.1
通讯作者：
Minghetti, L
中科院分区：
文献类型：
--
作者：
De Simone, R;Ajmone-Cat, MA;Minghetti, L
在中枢神经系统（CNS）中，细胞凋亡在发育过程中发挥着重要作用，是多种成人神经退行性疾病的主要致病机制。凋亡细胞死亡的一个主要特征是巨噬细胞和非专业吞噬细胞有效快速地清除垂死细胞，而不引起周围组织的炎症。凋亡细胞经历多种膜变化，包括所谓的“吃我”信号的外化，其同源受体存在于专业吞噬细胞上。在这些信号中，氨基磷脂磷脂酰丝氨酸（PS）似乎在防止巨噬细胞经典促炎症激活方面具有至关重要且独特的作用，从而确保凋亡细胞的沉默和安全清除。尽管在外周器官中进行了广泛的研究，但大脑中凋亡细胞的识别和清除过程直到最近才开始被阐明。在这里，我们总结了证据，表明在与表达 PS 的凋亡神经元相互作用时，小胶质细胞可能不再促进炎症级联反应，而是通过抗炎和神经保护功能促进受损神经元的消除。我们提出，通过激活静息和激活的小胶质细胞表达的特定 PS 受体 (PtdSerR) 诱导的抗炎小胶质细胞表型可能与神经退行性疾病的最终结果相关，其中细胞凋亡似乎发挥着至关重要的作用。
In the central nervous system (CNS), apoptosis plays an important role during development and is a primary pathogenic mechanism in several adult neurodegenerative diseases. A main feature of apoptotic cell death is the efficient and fast removal of dying cells by macrophages and nonprofessional phagocytes, without eliciting inflammation in the surrounding tissue. Apoptotic cells undergo several membrane changes, including the externalization of so-called "eat me" signals whose cognate receptors are present on professional phagocytes. Among these signals, the aminophospholipid phosphatidylserine (PS) appears to have a crucial and unique role in preventing the classical pro-inflammatory activation of macrophages, thus ensuring the silent and safe removal of apoptotic cells. Although extensively studied in the peripheral organs, the process of recognition and removal of apoptotic cells in the brain has only recently begun to be unraveled. Here, we summarize the evidence suggesting that upon interaction with PS-expressing apoptotic neurons, microglia may no longer promote the inflammatory cascade, but rather facilitate the elimination of damaged neurons through antiinflammatory and neuroprotective functions. We propose that the anti-inflammatory microglial phenotype induced through the activation of the specific PS receptor (PtdSerR), expressed by resting and activated microglial cells, could be relevant to the final outcome of neurodegenerative diseases, in which apoptosis seems to play a crucial role.