title: Macrophage migration inhibitory factor contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation.
abstract: BACKGROUND
  Macrophage migration inhibitory factor (MIF) is an inflammatory mediator released by macrophages that is central to the innate immune system, with an upstream role in the inflammatory cascade. MIF is one of the most important pathogenic factors in the development of the autoimmune diseases. In the current study, we investigated the role of MIF in anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation.
  
  
  METHODS
  Plasma levels of MIF from 31 patients with active ANCA-associated vasculitis (AAV) were analyzed by ELISA. The various effects of MIF in ANCA-induced neutrophil respiratory burst and degranulation were measured.
  
  
  RESULTS
  Plasma levels of circulating MIF were significantly higher in AAV patients with active disease compared with those in remission and healthy controls. Compared with MIF-primed neutrophils, the MFI value increased significantly in MIF-primed neutrophils further activated with MPO-ANCA-positive IgG or PR3-ANCA-positive IgG (270.8±9.7 vs. 421.5±9.7, P<0.001; 270.8±9.7 vs. 414.1±15.6, P<0.001, respectively). Compared with MIF-primed neutrophils, the lactoferrin concentration increased significantly in the supernatant of MIF-primed neutrophils further activated by MPO-ANCA-positive IgG (567.8±61.2ng/ml vs. 1677.0±42.5ng/ml, P<0.001) or PR3-ANCA-positive IgG (567.8±61.2ng/ml vs. 1546.0±116.2ng/ml, P<0.001), respectively. Interleukin-8 (IL-8), IL-6 and IL-23 were involved in ANCA-induced activation of MIF-primed neutrophils.
  
  
  CONCLUSIONS
  MIF primes neutrophils by increasing ANCA antigen translocation. The primed neutrophils can be further induced by ANCA, resulting in respiratory burst and degranulation.
authors.affiliation: Renal Division, Department of Medicine, The Affiliated Hospital of Inner Mongolia Medical College, Huhehot, Inner Mongolia 010050, China. Electronic address: Jian_hao8865@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Hao
authors.affiliation: Renal Division, Department of Medicine, The Affiliated Hospital of Inner Mongolia Medical College, Huhehot, Inner Mongolia 010050, China.
authors.forename: Tie-Gang
authors.initials: TG
authors.lastname: Lv
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Inner Mongolia Medical College, Huhehot, Inner Mongolia 010010, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Renal Division, Department of Medicine, The Affiliated Hospital of Inner Mongolia Medical College, Huhehot, Inner Mongolia 010050, China.
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Zhao
mesh_terms: D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D015550:Cell Degranulation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology*; D016897:Respiratory Burst
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: ANCA; Macrophage migration inhibitory factor; Neutrophils