Vascular smooth muscle cell-derived transforming growth factor-? promotes maturation of activated, neointima lesion-like macrophages.

ABSTRACT: To define the contribution of vascular smooth muscle cell (SMC)-derived factors to macrophage phenotypic modulation in the setting of vascular injury.By flow cytometry, macrophages (M4) were the predominant myeloid cell type recruited to wire-injured femoral arteries, in mouse, compared with neutrophils or eosinophils. Recruited macrophages from injured vessels exhibited a distinct expression profile relative to circulating mononuclear cells (peripheral blood monocytes; increased: interleukin-6, interleukin-10, interleukin-12b, CC chemokine receptor [CCR]3, CCR7, tumor necrosis factor-?, inducible nitric oxide synthase, arginase 1; decreased: interleukin-12a, matrix metalloproteinase [MMP]9). This phenotype was recapitulated in vitro by maturing rat bone marrow cells in the presence of macrophage-colony stimulating factor and 20% conditioned media from cultured rat SMC (sM?) compared with maturation in macrophage-colony stimulating factor alone (M0). Recombinant transforming growth factor (TGF)-?1 recapitulated the effect of SMC conditioned media. Macrophage maturation studies performed in the presence of a pan-TGF-? neutralizing antibody, a TGF-? receptor inhibitor, or conditioned media from TGF-?-depleted SMCs confirmed that the SMC-derived factor responsible for macrophage activation was TGF-?. Finally, the effect of SMC-mediated macrophage activation on SMC biology was assessed. SMCs cocultured with sM? exhibited increased rates of proliferation relative to SMCs cultured alone or with M0 macrophages.SMC-derived TGF-? modulates the phenotype of maturing macrophages in vitro, recapitulating the phenotype found in vascular lesions in vivo. SMC-modulated macrophages induce SMC activation to a greater extent than control macrophages.

SUBMITTER: Ostriker A 

PROVIDER: S-EPMC3966963 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature