title: Mouse aorta-derived mesenchymal progenitor cells contribute to and enhance the immune response of macrophage cells under inflammatory conditions.
abstract: BACKGROUND
  Mesenchymal progenitor cells interact with immune cells and modulate inflammatory responses. The cellular characteristics required for this modulation are under fervent investigation. Upon interaction with macrophage cells, they can contribute to or suppress an inflammatory response. Current studies have focused on mesenchymal progenitors derived from bone marrow, adipose, and placenta. However, the arterial wall contains many mesenchymal progenitor cells, which during vascular disease progression have the potential to interact with macrophage cells. To examine the consequence of vascular-tissue progenitor cell-macrophage cell interactions in an inflammatory environment, we used a recently established mesenchymal progenitor cell line derived from the mouse aorta.
  
  
  METHODS
  Mouse bone marrow-derived macrophage (MΦ) cells and mouse aorta-derived mesenchymal progenitor (mAo) cells were cultured alone or co-cultured directly and indirectly. Cells were treated with oxidized low-density lipoprotein (ox-LDL) or exposed to the inflammatory mediators lipopolysaccharide (LPS) and interferon-gamma (IFNγ) or both. A Toll-like receptor-4 (TLR4)-deficient macrophage cell line was used to determine the role of the mAo cells. To monitor inflammation, nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) secretions were measured.
  
  
  RESULTS
  Mesenchymal progenitor cells isolated from aorta and cloned by high proliferative capacity (mAo) can differentiate into multiple mesenchymal lineages and are positive for several commonly used mouse mesenchymal stem cell markers (that is, CD29, CD44, CD105, CD106, and Sca-1) but are negative for CD73 and ecto-5'-nucleotidase. In co-culture with MΦ cells, they increase MΦ oxidized-LDL uptake by 52.2%. In an inflammatory environment, they synergistically and additively contribute to local production of both NO and IL-6. After exposure to ox-LDL, the inflammatory response of MΦ cells to LPS and LPS/IFNγ is muted. However, when lipid-laden MΦ cells are co-cultured with mAo cell progenitors, the muted response is recovered and the contribution by the mAo cell progenitor is dependent upon cell contact.
  
  
  CONCLUSIONS
  The resident mesenchymal progenitor cell is a potential contributor to vascular inflammation when in contact with inflamed and lipid-laden MΦ cells. This interaction represents an additional target in vascular disease treatment. The potential for resident cells to contribute to the local immune response should be considered when designing therapeutics targeting inflammatory vascular disease.
authors.affiliation: Biomedical Research Core, Winthrop University Hospital, 222 Station Plaza North, Mineola, NY, 11501, USA. jevans@winthrop.org.|Stony Brook University School of Medicine, 222 Station Plaza North Suite 501, Mineola, NY, 11501, USA. jevans@winthrop.org.
authors.forename: Jodi F
authors.initials: JF
authors.lastname: Evans
authors.affiliation: Biomedical Research Core, Winthrop University Hospital, 222 Station Plaza North, Mineola, NY, 11501, USA. vjsalvador@winthrop.org.
authors.forename: Veronica
authors.initials: V
authors.lastname: Salvador
authors.affiliation: Biomedical Research Core, Winthrop University Hospital, 222 Station Plaza North, Mineola, NY, 11501, USA. sgeorge1@winthrop.org.
authors.forename: Sheela
authors.initials: S
authors.lastname: George
authors.affiliation: Biomedical Research Core, Winthrop University Hospital, 222 Station Plaza North, Mineola, NY, 11501, USA. ctrevino-gutierrez08@lions.molloy.edu.|Molloy College, 1000 Hempstead Avenue, Rockville Centre, NY, 11571, USA. ctrevino-gutierrez08@lions.molloy.edu.
authors.forename: Cristina
authors.initials: C
authors.lastname: Trevino-Gutierrez
authors.affiliation: Biomedical Research Core, Winthrop University Hospital, 222 Station Plaza North, Mineola, NY, 11501, USA. nunez09@lions.molloy.edu.|Molloy College, 1000 Hempstead Avenue, Rockville Centre, NY, 11571, USA. nunez09@lions.molloy.edu.
authors.forename: Catherine
authors.initials: C
authors.lastname: Nunez
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide; D007371:Interferon-gamma