Macrophage activation and polarization

Abstract

Macrophages are widely distributed immune system cells that play an indispensable role in homeostasis and defense. They can be phenotypically polarized by the microenvironment to mount specific functional programs. Polarized macrophages can be broadly classified in two main groups: classically activated macrophages (or M1), whose prototypical activating stimuli are IFNgamma and LPS, and alternatively activated macrophages (or M2), further subdivided in M2a (after exposure to IL-4 or IL-13), M2b (immune complexes in combination with IL-1beta or LPS) and M2c (IL-10, TGFbeta or glucocorticoids). M1 exhibit potent microbicidal properties and promote strong IL-12-mediated Th1 responses, whilst M2 support Th2-associated effector functions. Beyond infection M2 polarized macrophages play a role in resolution of inflammation through high endocytic clearance capacities and trophic factor synthesis, accompanied by reduced pro-inflammatory cytokine secretion. Similar functions are also exerted by tumor-associated macrophages (TAM), which also display an alternative-like activation phenotype and play a detrimental pro-tumoral role. Here we review the main functions of polarized macrophages and discuss the perspectives of this field.

Rabbit M1 and M2 macrophages can be induced by human recombinant GM‐CSF and M‐CSF

“…M1 macrophage has a higher expression of FcγRs and the ability to bind and uptake opsonized particles 26. The result from the current assay is not possible to distinguish internalized and cell surface‐adsorbed beads although the fluorescent images did show that larger numbers of latex beads were associated with G‐MΦ cells (M1) when comparing with those of M‐MΦ (M2).…”

Absence of a classically activated macrophage cytokine signature in peripheral spondylarthritis, including psoriatic arthritis

“…Of interest, this profile appeared to be more pronounced in patients with peripheral arthritis than in those with pure axial SpA (26). Based on the fact that IFN␥ is an important determinant of M1 polarization (2,3,(20)(21)(22) and on the association of synovial CD163ϩ M2 macrophages, but not T lymphocytes, with disease activity in peripheral SpA (9), the present study examined in more detail whether the presence of distinct macrophage subsets in both diseases is associated with different local inflammatory milieus.…”

“…A similar difference was observed for the prototypical M1 cytokine IL-12p70 in SpA versus RA synovitis (mean Ϯ SEM 5.5 Ϯ 1.7 pg/ml versus 15.2 Ϯ 6.6 pg/ml; P ϭ 0.090) (21). This was not restricted to cytokines, since the IFN␥-driven chemokine IP-10 produced by M1 (22) was also lower in SpA (mean Ϯ SEM 7.0 Ϯ 1.6 ng/ml versus 14.9 Ϯ 2.2 ng/ml in RA; P ϭ 0.006) ( Figure 2F). …”

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

“…Macrophages can differentiate from blood monocytes into two distinct subtypes, namely classically activated (M1) and alternatively activated (M2) macrophages endowed with effector or suppressive functions, respectively. 10,11 Macrophages infiltrating solid tumors (that is, tumor-associated macrophages or TAMs) share many characteristics with M2 macrophages and exert a pro-tumorigenic function in virtue of their direct or indirect (via cytokine production) immune-suppressive effects towards NK and T-cells. 12 In cancer patients, the presence of TAMs favors tumor progression.…”