title: Ex vivo and in vitro effect of serum amyloid a in the induction of macrophage M2 markers and efferocytosis of apoptotic neutrophils.
abstract: Macrophages affect the magnitude and duration of inflammatory response in a functionally heterogeneous manner. The phenotype of macrophages is maintained through a reversible homeostatic mechanism. A number of determinants that modulate macrophage plasticity have been identified, although the precise mechanisms are not fully understood. In this study, we report that stimulation of isolated human blood monocytes and mouse bone marrow-derived macrophages with human serum amyloid A (SAA), a major acute-phase protein, leads to induced expression of macrophage M2 markers, including IL-10, Ym1, Fizz-1, MRC1, IL-1Rn, and CCL17. The same effect was observed with macrophages exposed to SAA in peritoneal cavity. SAA also increases arginase 1 activity and enhances macrophage efferocytosis of apoptotic neutrophils in mouse macrophages. The induction of M2 markers requires MyD88 and the activation of multiple signaling pathways, but it is independent of Stat6. SAA induces IFN regulatory factor (IRF)4 expression and increases its DNA-binding activity. Silencing IRF4 by small interfering RNA abrogates SAA-induced expression of the M2 markers. These results suggest a potential role for SAA to alter macrophage phenotype and modulate macrophage functions through an MyD88-dependent mechanism that involves IRF4-mediated transcription.
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; and.
authors: Lei
authors: L
authors: Sun
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; and.
authors: Huibin
authors: H
authors: Zhou
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; and.
authors: Ziyan
authors: Z
authors: Zhu
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; and.
authors: Qian
authors: Q
authors: Yan
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; and.
authors: Lili
authors: L
authors: Wang
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; and.
authors: Qing
authors: Q
authors: Liang
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; and Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612 yedequan@sjtu.edu.cn.
authors: Richard D
authors: RD
authors: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D000685:Serum Amyloid A Protein