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F1000Prime Rep. 2014 Mar 3;6:13. doi: 10.12703/P6-13. eCollection 2014.

The M1 and M2 paradigm of macrophage activation: time for reassessment.

Author information

1
Botnar Research Center, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford Windmill Road, OX3 7LD, Oxford UK.
2
Sir William Dunn School of Pathology, University of Oxford South Parks Road, Oxford, OX1 3RE UK.

Abstract

Macrophages are endowed with a variety of receptors for lineage-determining growth factors, T helper (Th) cell cytokines, and B cell, host, and microbial products. In tissues, macrophages mature and are activated in a dynamic response to combinations of these stimuli to acquire specialized functional phenotypes. As for the lymphocyte system, a dichotomy has been proposed for macrophage activation: classic vs. alternative, also M1 and M2, respectively. In view of recent research about macrophage functions and the increasing number of immune-relevant ligands, a revision of the model is needed. Here, we assess how cytokines and pathogen signals influence their functional phenotypes and the evidence for M1 and M2 functions and revisit a paradigm initially based on the role of a restricted set of selected ligands in the immune response.

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