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

By F. Martínez, S. Gordon. F1000Prime Reports, 2014

4,278 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/006a4b8a4191f73633b3283403ffb705dcdd5e50

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In Immunology

Citations in the corpus

Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span (2017, background): “Macrophage polarization refers to distinct sets of inflammatory (M1) or fibrotic (M2) genes that are expressed by macrophages in cell culture that are first induced toward differentiation and then treated with LPS and IFN-γ or IL-4, respectively (Martinez and Gordon, 2014; Murray et al., 2014).”
Macrophages: development and tissue specialization. (2015, background): “The conceptual framework of macrophage activation hence requires reassessment to accommodate current findings (214).”
The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes (2018, background): “Macrophage phenotype readily changes based on spatiotemporal cues during wound healing, and several different subsets of macrophages, beyond the limited confines of simply M1 and M2 (Martinez and Gordon, 2014), have been defined depending on their cell surface markers, cytokine/growth factor/chemoki”
Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms (2015, methodology): “In the recent decade a model has been developed which describes the complex mechanism of macrophage activation as a polarization towards two opposite states, the M1 or classical, and the M2 or alternative activation [4, 8].”
The semantics of microglia activation: neuroinflammation, homeostasis, and stress (2021, background): “These findings suggest that chronic stress exposure does not cause microglia activation in a way that resembles the immunological origins of the term [32, 33, 158].”
Macrophage Polarization in Physiological and Pathological Pregnancy (2019, background): “It seems that NF-κB and STAT1 are the two major pathways involved in M1 macrophage polarization and result in microbicidal and tumouricidal functions (2, 4, 5, 15, 16).”
Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials (2015, background): “Classically activated macrophages, also called 1 acrophages, are produced during a cell-mediated immune response [30,31].”