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2015 ; 194
(10
): 4891-900
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English Wikipedia
Ex vivo and in vitro effect of serum amyloid a in the induction of macrophage M2
markers and efferocytosis of apoptotic neutrophils
#MMPMID25870242
Sun L
; Zhou H
; Zhu Z
; Yan Q
; Wang L
; Liang Q
; Ye RD
J Immunol
2015[May]; 194
(10
): 4891-900
PMID25870242
show ga
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.