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2011 ; 118
(26
): e192-208
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Transcriptomic analyses of murine resolution-phase macrophages
#MMPMID22012065
Stables MJ
; Shah S
; Camon EB
; Lovering RC
; Newson J
; Bystrom J
; Farrow S
; Gilroy DW
Blood
2011[Dec]; 118
(26
): e192-208
PMID22012065
show ga
Macrophages are either classically (M1) or alternatively-activated (M2). Whereas
this nomenclature was generated from monocyte-derived macrophages treated in
vitro with defined cytokine stimuli, the phenotype of in vivo-derived macrophages
is less understood. We completed Affymetrix-based transcriptomic analysis of
macrophages from the resolution phase of a zymosan-induced peritonitis. Compared
with macrophages from hyperinflamed mice possessing a pro-inflammatory nature as
well as naive macrophages from the uninflamed peritoneum, resolution-phase
macrophages (rM) are similar to monocyte-derived dendritic cells (DCs), being
CD209a positive but lacking CD11c. They are enriched for antigen
processing/presentation (MHC class II [H2-Eb1, H2-Ab1, H2-Ob, H2-Aa], CD74,
CD86), secrete T- and B-lymphocyte chemokines (Xcl1, Ccl5, Cxcl13) as well as
factors that enhance macrophage/DC development, and promote DC/T cell synapse
formation (Clec2i, Tnfsf4, Clcf1). rM are also enriched for cell
cycle/proliferation genes as well as Alox15, Timd4, and Tgfb2, key systems in the
termination of leukocyte trafficking and clearance of inflammatory cells.
Finally, comparison with in vitro-derived M1/M2 shows that rM are neither
classically nor alternatively activated but possess aspects of both definitions
consistent with an immune regulatory phenotype. We propose that macrophages in
situ cannot be rigidly categorized as they can express many shades of the
inflammatory spectrum determined by tissue, stimulus, and phase of inflammation.
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