title: Vascular smooth muscle cell-derived transforming growth factor-β promotes maturation of activated, neointima lesion-like macrophages.
abstract: OBJECTIVE
  To define the contribution of vascular smooth muscle cell (SMC)-derived factors to macrophage phenotypic modulation in the setting of vascular injury.
  
  
  RESULTS
  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-α, 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 (sMϕ) compared with maturation in macrophage-colony stimulating factor alone (M0). Recombinant transforming growth factor (TGF)-β1 recapitulated the effect of SMC conditioned media. Macrophage maturation studies performed in the presence of a pan-TGF-β neutralizing antibody, a TGF-β receptor inhibitor, or conditioned media from TGF-β-depleted SMCs confirmed that the SMC-derived factor responsible for macrophage activation was TGF-β. Finally, the effect of SMC-mediated macrophage activation on SMC biology was assessed. SMCs cocultured with sMϕ exhibited increased rates of proliferation relative to SMCs cultured alone or with M0 macrophages.
  
  
  CONCLUSIONS
  SMC-derived TGF-β 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.
authors: From the Department of Medicine, Division of Renal Diseases and Hypertension (H.N.H., J.P., M.C.M.W.-E., R.A.N.), Department of Pharmacology (A.O., M.C.M.W.-E., R.A.N.), and Cardiovascular and Pulmonary Research Laboratory (M.C.M.W.-E., R.A.N.), University of Colorado Denver, Aurora.
authors: Allison
authors: A
authors: Ostriker
authors: Henrick N
authors: HN
authors: Horita
authors: Joanna
authors: J
authors: Poczobutt
authors: Mary C M
authors: MC
authors: Weiser-Evans
authors: Raphael A
authors: RA
authors: Nemenoff
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008262:Macrophage Activation; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D058426:Neointima; D019899:Paracrine Communication; D010641:Phenotype; D034622:RNA Interference; D051381:Rats; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned; D016207:Cytokines; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016173:Macrophage Colony-Stimulating Factor; D048051:p38 Mitogen-Activated Protein Kinases
keywords: macrophages; muscle, smooth, vascular; neointima; transforming growth factor beta; vascular system injuries