The original alternatively activated macrophage was classified based on expression of the mannose receptor [8]; since then an assortment of different markers has been identified as ‘M2’ specific. One of the best characterized markers is the enzyme arginase 1 (Arg1) [25], which converts arginine to polyamines, proline, and ornithines that can contribute to wound healing and matrix deposition [26]. Interestingly, by using arginine, which is the same substrate used by iNOS, Arg1 can effectively outcompete iNOS to downregulate production of nitric oxide [27,28]. Thus, iNOS and Arg1 represent a relatively straightforward set of markers to follow M1 versus M2 phenotypes. Other markers used for identifying M2 cells include Ym1, a heparin-binding lectin [29,30], FIZZ1, which promotes deposition of extracellular matrix [31], and CD206, a mannose receptor [8]. A list of additional markers can been found in Table 1. Despite the benefit of having specific markers, using just one or two is limiting and ignores the overall diversity of M2 phenotypes.
