Macrophage Overexpressing NGAL Ameliorated Kidney Fibrosis in the UUO Mice Model

Cell Physiol Biochem. 2017;42(5):1945-1960. doi: 10.1159/000479835. Epub 2017 Aug 9.

Abstract

Background/aims: Alternatively activated macrophages (AAM) have regenerative and anti-inflammatory characteristics. Here, we sought to evaluate whether AAM cell therapy reduces renal inflammation and fibrosis in the unilateral ureteral obstruction (UUO) mice model.

Methods: We stabilized macrophages by adenoviral vector NGAL (Neutrophil gelatinase-associated lipocalin-2) and infused them into UUO mice. To ascertain whether macrophages were capable of reaching the obstructed kidney, macrophages were stained and detected by in vivo cell tracking.

Results: We demonstrated that some infused macrophages reached the obstructed kidney and that infusion of macrophages overexpressing NGAL was associated with reduced kidney interstitial fibrosis and inflammation. This therapeutic effect was mainly associated with the phenotype and function preservation of the transferred macrophages isolated from the obstructed kidney Conclusions: Macrophage plasticity is a major hurdle for achieving macrophage therapy success in chronic nephropathies and could be overcome by transferring lipocalin-2.

Keywords: Alternatively activated macrophages; Chronic kidney disease; Macrophage plasticity.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • B7-2 Antigen / genetics
  • B7-2 Antigen / metabolism
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism
  • Cells, Cultured
  • Disease Models, Animal
  • Fibrosis
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Kidney / pathology*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Lipocalin-2 / genetics
  • Lipocalin-2 / metabolism*
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Macrophages / transplantation
  • Male
  • Mannose Receptor
  • Mannose-Binding Lectins / genetics
  • Mannose-Binding Lectins / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Ureteral Obstruction / metabolism
  • Ureteral Obstruction / pathology
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • B7-2 Antigen
  • CD40 Antigens
  • Lectins, C-Type
  • Lipocalin-2
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Transforming Growth Factor beta1
  • beta-Galactosidase
  • Matrix Metalloproteinase 9