A tissue macrophage will continuously adjust its expression of surface receptor proteins and secreted products in response to local stimuli, in a manner so similar to the T lymphocytes of the adaptive immune branch that the “Th1 vs. Th2” nomenclature has been adopted to classify macrophage activation as “M1 vs. M2.” “M1” activation describes a macrophage performing “classical” anti-microbial functions, while “M2” activation encompasses the “alternative,” quite literally, everything else— from helminth defense, to tissue repair in the wake of an oxidative burst, to feed-back regulation of the immune system.
M1 is to macrophages as Th1 is to lymphocytes; among other cytokines, Th1 cells can produce high levels of IFN-γ, an extremely potent macrophage chemoattractant, and also one of the most potent endogenous M1 macrophage activation stimuli. LPS (endotoxin) from bacteria can also stimulate M1 macrophages through TLR-4, and it is the most well described exogenous M1 stimuli. A macrophage so stimulated will produce high levels of TNF-α, IL-6 and IL-12, which have a variety of effects on stromal tissue cells. In addition to cytokine production, M1 activation stimulates iNOS (inducible nitric oxide synthetase)activity and phagocytosis, i.e. macrophages become better at consuming and destroying bacteria.
Similar to the M1 story, M2 is to macrophages as Th2 is to lymphocytes; Th2 cells can produce high levels of IL-4. IL-4 greatly stimulates the expression of mannose receptor, which is an opsonin (antibody)-independent cell surface particle receptor (or pattern-recognition receptor) and is widely accepted as the canonical marker for M2 macrophages. M2 activation also results in increased CD36 expression, which binds to oxidized low density lipoproteins, thrombospondin, and several other molecules. The increased levels of these scavenger receptor proteins on M2 macrophages is consistent with the need to clean out debris in order to successfully resolve, or end, an inflammatory response. Another role for the M2 activated macrophage is to react against invasion by helminth worms or other parasites. Accordingly, IL-4 stimulates the increased expression of acidic mammalian chitinase (AMCase), our only enzyme which can hydrolyze the shells of worm eggs into digestible and MHC Class II-presentable proteins.
This post was written for us by Jason Fritz, a PhD candidate in the School of Pharmacy, who took IMMU 7630 2 years ago and is the macrophage king!
M1 is to macrophages as Th1 is to lymphocytes; among other cytokines, Th1 cells can produce high levels of IFN-γ, an extremely potent macrophage chemoattractant, and also one of the most potent endogenous M1 macrophage activation stimuli. LPS (endotoxin) from bacteria can also stimulate M1 macrophages through TLR-4, and it is the most well described exogenous M1 stimuli. A macrophage so stimulated will produce high levels of TNF-α, IL-6 and IL-12, which have a variety of effects on stromal tissue cells. In addition to cytokine production, M1 activation stimulates iNOS (inducible nitric oxide synthetase)activity and phagocytosis, i.e. macrophages become better at consuming and destroying bacteria.
Similar to the M1 story, M2 is to macrophages as Th2 is to lymphocytes; Th2 cells can produce high levels of IL-4. IL-4 greatly stimulates the expression of mannose receptor, which is an opsonin (antibody)-independent cell surface particle receptor (or pattern-recognition receptor) and is widely accepted as the canonical marker for M2 macrophages. M2 activation also results in increased CD36 expression, which binds to oxidized low density lipoproteins, thrombospondin, and several other molecules. The increased levels of these scavenger receptor proteins on M2 macrophages is consistent with the need to clean out debris in order to successfully resolve, or end, an inflammatory response. Another role for the M2 activated macrophage is to react against invasion by helminth worms or other parasites. Accordingly, IL-4 stimulates the increased expression of acidic mammalian chitinase (AMCase), our only enzyme which can hydrolyze the shells of worm eggs into digestible and MHC Class II-presentable proteins.
