Phagocytosis of apoptotic inflammatory cells by microglia and its therapeutic implications: Termination of CNS autoimmune inflammation and modulation by interferon-beta
Phagocytosis of apoptotic inflammatory cells by microglia and its therapeutic implications: Termination of CNS autoimmune inflammation and modulation by interferon-beta
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作者：
Chan, A;Seguin, R;Gold, R
CNS中自身侵袭性T细胞的凋亡是解决T细胞浸润的有效非炎症机制，有助于T细胞介导的神经炎性疾病的临床恢复。组织特异性吞噬细胞对凋亡白细胞的清除在炎症浸润的消退中至关重要，并导致吞噬细胞免疫功能的显著下调。将来自手术切除的正常脑组织的成人小胶质细胞用于凋亡的自体外周血来源的单核细胞（MNC）的标准化、光显微镜体外吞噬测定。来自五个不同的患者的小胶质细胞有一个高的能力，凋亡的MNCs的摄取与非凋亡的靶细胞的吞噬率为非凋亡的MNCs的凋亡的MNCs只有61.6%。一种新描述的磷脂酰丝氨酸受体，在巨噬细胞吞噬凋亡细胞中起关键作用，也在人类小胶质细胞上以相似的水平表达。使用刘易斯大鼠小胶质细胞和凋亡的、致脑炎的、髓鞘碱性蛋白特异性自体T细胞研究了治疗用免疫调节剂干扰素β（IFN β）的作用。此外，大鼠小胶质细胞具有高的吞噬凋亡的T细胞的能力。IFN β使凋亡T细胞的吞噬作用增加至未处理对照组的36.8%。增强的吞噬活性对凋亡T细胞具有选择性，并且不通过增加的IL-10分泌介导。在自身免疫性炎症的人CNS中，小胶质细胞可以有效和快速地清除凋亡的炎症细胞。在体外增加的吞噬作用的IFN β值得进一步研究是否这种机制也可以治疗利用。(C)2003年威利-利斯。
Apoptosis of autoaggressive T-cells in the CNS is an effective, noninflammatory mechanism for the resolution of T-cell infiltrates, contributing to clinical recovery in T-cell-mediated neuroinflammatory diseases. The clearance of apoptotic leukocytes by tissue-specific phagocytes is critical in the resolution of the inflammatory infiltrate and leads to a profound downregulation of phagocyte immune functions. Adult human microglia from surgically removed normal brain tissue was used in a standardized, light-microscopic in vitro phagocytosis assay of apoptotic autologous peripheral blood-derived mononuclear cells (MNCs). Microglia from five different patients had a high capacity for the uptake of apoptotic MNCs in contrast to nonapoptotic target cells with the phagocytosis rate for nonapoptotic MNCs amounting to only 61.6% of the apoptotic MNCs. A newly described phosphatidylserine receptor, critical in the phagocytosis of apoptotic cells by macrophages, is also expressed at similar levels on human microglia. The effects of the therapeutically used immunomodulatory agent interferonbeta (IFNbeta) were investigated using Lewis rat microglia and apoptotic, encephalitogenic, myelin basic protein-specific autologous T-cells. Also, rat microglia had a high capacity to phagocytose apoptotic T-cells specifically. IFNbeta increased the phagocytosis of apoptotic T-cells to 36.8% above the untreated controls. The enhanced phagocytic activity was selective for apoptotic T-cells and was not mediated by increased IL-10 secretion. Apoptotic inflammatory cells may be efficiently and rapidly removed by microglial cells in the autoimmune-inflamed human CNS. The in vitro increase of phagocytosis by IFNbeta merits further investigations whether this mechanism could also be therapeutically exploited. (C) 2003 Wiley-Liss.