Macrophages are heterogeneous immune cells that exhibit a high plasticity and can be roughly classified by two polarized end states named M1 (proinflammatory) and M2 (antiinflammatory) ( 1).
In absence of G2A the macrophages are localized in an antiinflammatory microenvironment and macrophage polarization is shifted toward M2-like macrophages. Taken together, G2A is necessary to position macrophages in the proinflammatory microenvironment surrounding the center of inflammation. Fittingly neutrophil efferocytosis was decreased in G2A-deficient mice and several lipids, which are released by neutrophils and promote G2A-mediated chemotaxis, were increased in the inflamed tissue.
While the number of monocyte-derived macrophages in the inflamed paw was not altered, G2A-deficient mice had less macrophages in the direct vicinity of the origin of inflammation, an area marked by the presence of zymosan, neutrophil accumulation and proinflammatory cytokines. However, G2A activation was not sufficient to promote M1-polarization in bone marrow-derived macrophages. Fittingly, the number of M1-like macrophages was reduced in the inflamed tissue in G2A-deficient mice. G2A-deficient mice showed a reduced zymosan-induced thermal hyperalgesia, which was reversed after macrophage depletion. Here, we studied the role of the G-protein coupled receptor G2A (GPR132), in chemotactic migration and polarization of macrophages, using the zymosan-model of acute inflammation. Macrophages are highly versatile cells, which acquire, depending on their microenvironment, pro- (M1-like), or antiinflammatory (M2-like) phenotypes.
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