Glucocorticoid augmentation of macrophage capacity for phagocytosis of apoptotic cells is associated with reduced p130Cas expression, loss of paxillin/pyk2 phosphorylation, and high levels of active Rac
Glucocorticoid augmentation of macrophage capacity for phagocytosis of apoptotic cells is associated with reduced p130Cas expression, loss of paxillin/pyk2 phosphorylation, and high levels of active Rac
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DOI：
10.4049/jimmunol.167.2.976
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发表时间：
2001-07-15
影响因子：
4.4
通讯作者：
Dransfield, I
中科院分区：
文献类型：
--
作者：
Giles, KM;Ross, K;Dransfield, I
凋亡粒细胞的吞噬清除在确定炎症结果、与纤维化修复机制和/或自身免疫应答的发展相关的慢性状态的消退或进展中具有关键作用。在这项研究中，我们描述了重编程的单核细胞巨噬细胞分化的糖皮质激素，导致其吞噬凋亡的中性粒细胞的能力显着增强。这种单核细胞/巨噬细胞表型的特征在于磷酸化减少，因此招募桩蛋白和pyk 2的焦点接触和下调p130 Cas，整合素粘附信号传导中的关键衔接分子。糖皮质激素处理的细胞也显示出更高水平的活性Rac和细胞骨架活性，这反映了凋亡中性粒细胞的吞噬能力增加。我们建议糖皮质激素诱导的细胞骨架元素重组能力的变化对于凋亡细胞的有效吞噬摄取是必不可少的。
Phagocytic clearance of apoptotic granulocytes has a pivotal role in determining an inflammatory outcome, resolution or progression to a chronic state associated with development of fibrotic repair mechanisms, and/or autoimmune responses. In this study, we describe reprogramming of monocyte to macrophage differentiation by glucocorticoids, resulting in a marked augmentation of their capacity for phagocytosis of apoptotic neutrophils. This monocyte/macrophage phenotype was characterized by decreased phosphorylation, and therefore recruitment of paxillin and pyk2 to focal contacts and a down-regulation of p130Cas, a key adaptor molecule in integrin adhesion signaling. Glucocorticoid-treated cells also displayed higher levels of active Rac and cytoskeletal activity, which were mirrored by increases in phagocytic capability for apoptotic neutrophils. We propose that changes in the capacity for reorganization of cytoskeletal elements induced by glucocorticoids are essential for efficient phagocytic uptake of apoptotic cells.