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Abstract
The daily clearance of physiologically dying cells is performed safely mainly by cells in the mononuclear phagocyte system. They can recognize and engulf dying cells utilizing several cooperative mechanisms. In our study we show that the expression of a broad range of apopto-phagocytic genes is strongly up-regulated during differentiation of human monocytes to macrophages with different donor variability. The glucocorticoid dexamethasone has a profound effect on this process by selectively up-regulating six genes and down-regulating several others. The key role of the up-regulated mer tyrosine kinase (Mertk) in dexamethasone induced enhancement of phagocytosis could be demonstrated in human monocyte derived macrophages by gene silencing as well as blocking antibodies, and also in a monocyte-macrophage like cell line. However, the additional role of other glucocorticoid induced elements must be also considered since the presence of autologous serum during phagocytosis could almost completely compensate for the blocked function of Mertk.
Highlights
The efficient elimination of apoptotic cells or those dying through necrosis is performed mainly by the cells of the mononuclear phagocyte system [1,2]
We observed an increase from 8.3% to 32.4% in phagocytosis of apoptotic neutrophils by differentiated macrophages compared to monocytes [19]
There was a heterogenous group of genes with high level of expression in monocytes that did not change during differentiation: TGFB1, PECAM1, CD14, THBS1, CAPN 1 and 2, RHOG, ANXA1, PYCARD, ITGAX
Summary
The efficient elimination of apoptotic cells or those dying through necrosis is performed mainly by the cells of the mononuclear phagocyte system [1,2]. The process of apoptotic cell corpse removal by professional phagocytes is remarkably complex and only partly defined [4,5,6]. It consists of two major steps: (1) recognition and (2) subsequent engulfment of apoptotic cells [1]. Ligands appearing on the apoptotic cells, receptors on the phagocyte and bridging molecules in the environment may act to drive either or both of these steps [7,33]. While elements of the recognition and receptor elements of the apopto-phagocytic machinery seem to be highly redundant [8], the signaling pathways for the engulfing machinery converge to switch on rac dependent cytoskeletal processes [7]
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