The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation.
The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation.
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DOI：
10.1007/s00281-016-0555-3
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发表时间：
2016-07
影响因子：
9
通讯作者：
Hussell T
中科院分区：
文献类型：
--
作者：
Grabiec AM;Hussell T
肺中的急性和慢性炎症反应与大量经历凋亡的免疫和结构细胞的积累有关，这些细胞需要在称为"巨噬细胞吞噬"的过程中被吞噬细胞吞噬。凋亡细胞的识别和从肺中的去除主要由气道巨噬细胞介导，尽管未成熟的树突状细胞和非专职吞噬细胞，如上皮细胞和间充质细胞，也可以显示这种功能。从气道有效清除凋亡细胞对于成功解决炎症和恢复肺内稳态是必不可少的。该过程的破坏导致累积的凋亡细胞的继发性坏死、坏死细胞碎片的释放以及随后通过释放的"损伤相关分子模式"（DAMPS）对先天免疫系统的不受控制的炎症激活。为了控制免疫应答的持续时间并防止自身免疫反应，在吞噬细胞中在凋亡细胞摄取时启动抗炎信号级联，由一系列识别凋亡细胞外化或分泌的特异性磷脂或蛋白质的受体介导。然而，凋亡细胞识别受体（例如受体酪氨酸激酶Tyro3、Axl和MerTK（TAM）家族）的延长激活可延迟或防止对后续感染的炎症反应。在这篇综述中，我们将讨论最近的进展，在我们的理解机制控制凋亡细胞识别和清除从肺内稳态和炎症过程中，有缺陷的白细胞增多症的贡献慢性炎症性肺病，如慢性阻塞性肺病，哮喘和囊性纤维化，和影响的信号引发的凋亡细胞在肺部微生物感染的易感性。
Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called ‘efferocytosis’. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released ‘damage associated molecular patterns’ (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections.