title: Structure and function of renal macrophages and dendritic cells from lupus-prone mice.
abstract: OBJECTIVE
  To characterize renal macrophages and dendritic cells (DCs) in 2 murine models of lupus nephritis.
  
  
  METHODS
  We used a bead-based enrichment step followed by cell sorting to isolate populations of interest from young mice and nephritic mice. Cell morphology was examined by microscopy. Arginase and nitrite production was examined using biochemical assays. The antigen-presenting functions of the cells were determined using mixed lymphocyte reactions. Selected cytokine, chemokine, and Toll-like receptor (TLR) profiles were examined using real-time quantitative polymerase chain reaction.
  
  
  RESULTS
  We identified 2 populations of macrophages and 3 populations of DCs in both of our murine models of lupus (NZB/NZW and [NZW × BXSB]F1 mice). F4/80(high) macrophages, which were resident in normal kidneys and found to be increased in number during nephritis, did not produce either arginase or nitrite upon cytokine stimulation and acquired a mixed proinflammatory and antiinflammatory functional phenotype during nephritis that resembles the constitutively activated phenotype of gut F4/80(high) macrophages. The various cell types differed in their expression of chemokine receptors and TLRs, consistent with variability in their renal location. Resident renal CD103+ DCs were the best antigen-presenting cells and could easily be distinguished from CD11c(high) myeloid DCs that accumulated in large numbers during nephritis.
  
  
  CONCLUSIONS
  Our study highlights the heterogeneity of the macrophage/DC infiltrate in chronic lupus nephritis and provides an initial phenotypic and functional analysis of the different cellular components that can now be used to define the role of each cell subset in nephritis progression or amelioration. Of note, the dominant macrophage population that accumulates during nephritis has an acquired phenotype that is neither M1 nor M2 and may reflect failure of resolution of inflammation.
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Sahu
authors.forename: Ramalingam
authors.initials: R
authors.lastname: Bethunaickan
authors.forename: Satwinder
authors.initials: S
authors.lastname: Singh
authors.forename: Anne
authors.initials: A
authors.lastname: Davidson
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D003713:Dendritic Cells / Q000473:pathology* / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007668:Kidney / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010641:Phenotype
chemical_list: D052247:Nitric Oxide Synthase Type II; D001119:Arginase