Identification of conserved M2 alternative activation markers in human and mouse. Fold regulation of M2 versus M0 macrophages plotted for each dataset. (A) Pairwise comparisons of human samples follow an inclined ellipse contour, with many genes up- or down-regulated by IL-4 in common. (B) Comparison of proteomics data shows a more spread distribution. (C) Genes up-regulated or down-regulated by IL-4 in all human samples and coincidences between microarray and proteomics. (D-E) Pairwise comparisons of mouse samples. The plots for gene (D) and protein (E) expression analysis follow similar patterns as human samples. (F) Microarrays and proteomics of mouse samples. Genes consistently up-regulated or down-regulated by IL-4 and coincidences between microarray and proteomics are shown. (G) Scatter plots of comparisons of human and mouse microarray profiles show star-like rather than inclined ellipse-like contours. The coincidences of genes regulated in macrophages from both species consisted of 35 genes. (H) With proteomics, the coincidences amounted to 65 proteins. (I) Comparing the regulation of transcripts and proteins, only one gene was consistently induced by IL-4: TGM2. (J) K means clustering of genes modulated by IL-4 in human macrophages in macrophages stimulated with M-CSF, IL-10, and IFN-γ. (K) Alternative activation profile conserved in the human and the mouse organized into 3 and 4 gene and protein expression networks (top and bottom, respectively). At the center of the networks is the highly connected TGM2. The networks comprise key gene-expression regulators and signaling mediators. Expression ranking is pseudocolored in red for up-regulated and green for down-regulated genes and is influenced by key regulators of macrophage activation (selected in turquoise; the rest are in white). Label color: red indicates; green, down-regulated; and black, regulator. Label size is for highlighting purposes.