|View The Complex Biology of Macrophages Poster showing the Expression Levels of Different Macrophage Markers|
Following development, macrophages encounter diverse stimuli, which can alter their transcriptional programs leading to an activated state. The classic view of macrophage activation is described in a dichotomous model. According to this model, classical (M1) macrophage activation is induced by IFN-gamma or lipopolysaccharide (LPS) and promotes a pro-inflammatory response, while alternative (M2) macrophage activation is induced by IL-4, IL-10, or IL-13 and stimulates an anti-inflammatory response. Slight phenotypic variations noted in the M2 phenotype led to the description of different M2 subsets known as M2a, M2b, M2c, M2d, which were defined based on the stimuli used for activation. It has been widely recognized however, that even this expanded model of macrophage activation is too simple to account for the range of phenotypes observed in macrophages under different conditions. For this reason, a new multidimensional model of macrophage activation has been proposed. This model suggests that a spectrum of activation states spanning the M1/M2 states can occur in response to diverse signals including ontogeny-related signals, tissue-specific signals, and stress signals, which are integrated to determine the macrophage response.