M1 M2a M2b M2c
Stimulation/activation IFN-γ IL4/IL13 ICs IL-10
TNF-α   LPS TGF-β
LPS   TLRinteractions GCs
Expression CD86 CD163 CD86 CD163
CD80 SR    
IL-1R 1 CD206    
TLR2 IL-1R ii    
TLR4 Mouse only:    
iNOS Ym1    
MR Fizz1    
  Arg-1    
Cytokines TNF-α IL-10 IL-1 IL-10
TNFSF1A TGF-β IL-10 TGF-β
IL-1β IL-1ra    
IL-6      
IL-8      
IL-12      
IL-23      
Chemokines when activated CCL10 CCL18    
CCL9 CCL22    
CCL5 CCL24    
CCL4      
CCL3      
CCL2      
CXCL 10      
Enzymes Tissue degrading collagenase Tissue Remodelling and repair    
Matrix Proteinases (MMP2, MMP9, Plasminogen activator) TIMP1    
  PDGF    
Table 1: M1 and M2 subgroups. Macrophages are subdivided into the M1 classically activated and the M2 alternative activated subsets. M1 macrophages are stimulated by INF-γ, TNF-α and LPS which leads to cytokine production of TNF-α, IL-1β, IL-6, IL-8, IL-12, IL-23, CCL2, CCL3, CCL4, CCL5, CCL9 and CCL10. The M1 markers expressed include CD86, CD80, TLR2 and 4 along with iNOS and stimulate tissue degradation by secretion of enzymes such as collagenases and matrixproteinases [135]. In contrast, M2 macrophages express the scavenger receptors (SR), mannose receptor CD206 and CD163 and produce IL-10, IL1ra, CCL18, CCL22 and CCL24 and are involved in tissue remodelling and repair by secretion of TIMP1 and PDGF. The M1 subset is inhibited by IL-4 and IL-10 while the M2 subset is inhibited by IFN- γ [135].