Alternatively activated macrophages as therapeutic agents for kidney disease: in vivo stability is a key factor  Senthilkumar Alagesan, Matthew D. Griffin  Kidney International  Volume 85, Issue 4, Pages 730-733 (April 2014) DOI: 10.1038/ki.2013.405 Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 1 Outline of differentiation pathways and potential polarization fates of naturally occurring and in vitro–generated mouse macrophages. Top and middle: A simplified schematic of the stages and key driving factors for in vivo macrophage (M0) differentiation within tissue and of polarization to M1- or M2-type activation states. Upper right: The strategy of generating M2-like alternatively activated macrophages (AAMs) in vitro from multiple potential precursors. Gray-shaded oval: The potential reported by Cao et al. for in vitro–generated AAMs to lose efficacy through CSF-1-driven proliferation and depolarization.9 Boxes at the bottom: Summary of the differential markers and effector molecules and tissue effects of M1- and M2-polarized macrophages based primarily on literature from mouse studies.2,3,5,10 AAM, alternatively activated macrophage; CCL, CC-chemokine ligand; COX2, cyclooxygenase 2; CSF-1, colony-stimulating factor-1; FIZZ1, found in inflammatory zone-1; IFN-γ, interferon-γ; IL, interleukin; iNOS, inducible nitric oxide synthase; IRF4, interferon regulatory factor 4; KLF4, Krüppel-like factor 4; MARCO, macrophage receptor with collagenous structure; PPAR, peroxisome proliferator–activated receptor; SOCS, suppressor of cytokine signaling; TGF-β, transforming growth factor-β; Th, T-helper cell; TLR, toll-like receptor; TNF-α, tumor necrosis factor-α. Kidney International 2014 85, 730-733DOI: (10.1038/ki.2013.405) Copyright © 2014 International Society of Nephrology Terms and Conditions