title: Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus.
abstract: OBJECTIVE
  Macrophages have recently been shown to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying mechanisms remain unclear.
  
  
  METHODS
  Here, we used an activated lymphocyte-derived DNA (ALD-DNA) method to induce SLE in mice. We used a macrophage-specific eliminator clodronate to selectively deplete macrophages in mice. We isolated macrophages from bone marrow of the mice and used cytokines to differentiate M1 and M2 macrophages, respectively. Adoptive transplantation of M1 or M2 macrophages was performed in clodronate-treated mice. The effects on SLE were evaluated by serum anti-dsDNA autoantibody, by renal pathological changes, and by urine protein levels.
  
  
  RESULTS
  ALD-DNA induced SLE-like features in mice, manifested by induction of serum anti-dsDNA autoantibody, by renal pathological changes, and by increases in urine protein levels. Clodronate significantly decreased macrophages in mice, which significantly increased SLE severity. Adoptive transplantation of M2, but not M1 macrophages significantly reduced SLE severity in clodronate- and ALD-DNA-treated mice.
  
  
  CONCLUSIONS
  M1 and M2 macrophages play different roles in development of SLE. M1 macrophages increase the severity of SLE, while M2 macrophages reduce it. Modulation of macrophage polarity may be an attractive therapy for SLE.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhu
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D016764:Cell Polarity; D002478:Cells, Cultured; D004002:Clodronic Acid / Q000378:metabolism; D004247:DNA / Q000276:immunology*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D000974:Antibodies, Antinuclear; D004002:Clodronic Acid; D007371:Interferon-gamma; D004247:DNA