Macrophage polarization

This ability is connected to their multiple roles in the organism: they are powerful effector cells of the innate immune system, but also important in removal of cellular debris, embryonic development and tissue repair.

This broad classification was based on in vitro studies, in which cultured macrophages were treated with molecules that stimulated their phenotype switching to a particular state.

[2] In addition to chemical stimulation, it has been shown that the stiffness of the underlying substrate a macrophage is grown on can direct polarization state, functional roles and migration mode.

[9] Macrophage activation spectrum is thus considered to be wider, involving complex regulatory pathway to response to plethora of different signals from the environment.

A number of studies have shown that bacterial infection induces polarization of macrophages toward the M1 phenotype, resulting in phagocytosis and intracellular killing of bacteria in vitro and in vivo.

[25] Improper and untimely control of M1 macrophage-mediated inflammatory response can lead to disruption of normal tissue homeostasis and impede vascular repair.

[27] In order to counteract the inflammatory response, macrophages undergo apoptosis or polarize to an M2 phenotype to protect the host from the excessive injury.

[28] It is shown in vitro that macrophage treatment with IL-4 and IL-13 leads to inhibition of pro-inflammatory signals production and upregulation of scavenging mannose receptor CD206.

Regulatory macrophages were described to have anti-inflammatory properties, which are important in resolutive phases of the inflammation, producing the immunosuppressive cytokine IL-10.

On the other side, wound healing macrophages were shown to produce IL-4 and upregulate arginase activity, which is the enzyme enrolled in production of polyamines and collagen, thus regenerating the damaged tissue.

[7][12] M2a macrophages are activated by IL-4 and IL-13 which evokes upregulated expression of arginase-1, mannose receptor MRc1 (CD206), antigen presentation by MHC II system, and production of IL-10 and TGF-𝛽, leading to tissue regeneration and internalization of pro-inflammatory molecules to prevent the inflammatory response.

M2c macrophages are activated by IL-10, transforming growth factor beta (TGF-𝛽) and glucocorticoids, and produce IL-10 and TGFβ, leading to suppression of inflammatory response.