Macrophage polarization
From Wikipedia, the free encyclopedia
Macrophage polarization is a process by which macrophages adopt different functional programs in response to the signals from their microenvironment. 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.[1]
By simplified classification, macrophage phenotype has been divided into 2 groups: M1 (classically activated macrophages) and M2 (alternatively activated macrophages). 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.[3] A continuum of M1-M2 polarization may arise even in the absence of polarizing cytokines and differences in substrate stiffness.[4] M1 macrophages were described as the pro-inflammatory type, important in direct host-defense against pathogens, such as phagocytosis and secretion of pro-inflammatory cytokines and microbicidal molecules. M2 macrophages were described to have quite the opposite function: regulation of the resolution phase of inflammation and the repair of damaged tissues. Later, more extensive in vitro and ex vivo studies have shown that macrophage phenotypes are much more diverse, overlapping with each other in terms of gene expression and function, revealing that these many hybrid states form a continuum of activation states which depend on the microenvironment.[5][6][7][8] Moreover, in vivo, there is a high diversity in gene expression profile between different populations of tissue macrophages.[9] Macrophage activation spectrum is thus considered to be wider, involving complex regulatory pathway to response to plethora of different signals from the environment.[10][11] The diversity of macrophage phenotypes still remain to be fully characterized in vivo.
The imbalance of the macrophage types is related to a number of immunity-related diseases.[12][13] For example, it has been shown that increased M1/M2 ratio correlates with development of inflammatory bowel disease,[14][15] as well as obesity in mice.[16][17][18] On the other side, in vitro experiments implicated M2 macrophages as the primary mediators of tissue fibrosis.[13] Several studies have associated the fibrotic profile of M2 macrophages with the pathogenesis of systemic sclerosis.[12][19]