Macrophages (MPhis) exhibit functional
heterogeneity and plasticity in the local microenvironment. Recently, it was reported that MPhis can be divided into
proinflammatory MPhis (MPhi1) and
anti-inflammatory MPhis (MPhi2) based on their
polarized functional properties. Here, we report that
nicotine, the major ingredient of
cigarette smoke, can modulate the characteristics of MPhi1. Granulocyte-macrophage colony-stimulating factor-driven MPhi1 with
nicotine (Ni-MPhi1) showed the
phenotypic characteristics of MPhi2. Like MPhi2, Ni-MPhi1 exhibited antigen-uptake activities. Ni-MPhi1 suppressed IL-12, but maintained IL-10 and produced high amounts of
MCP-1 upon
lipopolysaccharide stimulation compared with MPhi1. Moreover, we observed strong proliferative responses of
T cells to lipopolysaccharide-stimulated MPhi1, whereas Ni-MPhi1 reduced
T cell proliferation and inhibited
IFN-gamma production by
T cells. These results suggest that
nicotine can change the functional characteristics of MPhi and skew the MPhi1
phenotype to MPhi2. We propose that
nicotine is a potent regulator that modulates
immune responses in microenvironments.
