title: Differential role of lipocalin 2 during immune complex-mediated acute and chronic inflammation in mice.
abstract: OBJECTIVE
  Lipocalin 2 (LCN-2) is an innate immune protein that is expressed by a variety of cells and is highly up-regulated during several pathologic conditions, including immune complex (IC)-mediated inflammatory/autoimmune disorders. However, the function of LCN-2 during IC-mediated inflammation is largely unknown. Therefore, this study was undertaken to investigate the role of LCN-2 in IC-mediated diseases.
  
  
  METHODS
  The up-regulation of LCN-2 was determined by enzyme-linked immunosorbent assay in 3 different mouse models of IC-mediated autoimmune disease: systemic lupus erythematosus, collagen-induced arthritis, and serum-transfer arthritis. The in vivo role of LCN-2 during IC-mediated inflammation was investigated using LCN-2-knockout mice and their wild-type littermates.
  
  
  RESULTS
  LCN-2 levels were significantly elevated in all 3 of the autoimmune disease models. Further, in an acute skin inflammation model, LCN-2-knockout mice exhibited a 50% reduction in inflammation, with histopathologic analysis revealing notably reduced immune cell infiltration as compared to wild-type mice. Administration of recombinant LCN-2 to LCN-2-knockout mice restored inflammation to levels observed in wild-type mice. Neutralization of LCN-2 using a monoclonal antibody significantly reduced inflammation in wild-type mice. In contrast, LCN-2-knockout mice developed more severe serum-induced arthritis compared to wild-type mice. Histologic analysis revealed extensive tissue and bone destruction, with significantly reduced neutrophil infiltration but considerably more macrophage migration, in LCN-2-knockout mice compared to wild-type mice.
  
  
  CONCLUSIONS
  These results demonstrate that LCN-2 may regulate immune cell recruitment to the site of inflammation, a process essential for the controlled initiation, perpetuation, and resolution of inflammatory processes. Thus, LCN-2 may present a promising target in the treatment of IC-mediated inflammatory/autoimmune diseases.
authors.affiliation: Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic Medicine, Suwanee, Georgia 30024, USA. rangaiahsh@pcom.edu
authors.forename: Rangaiah
authors.initials: R
authors.lastname: Shashidharamurthy
authors.forename: Deepa
authors.initials: D
authors.lastname: Machiah
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Aitken
authors.forename: Kalyani
authors.initials: K
authors.lastname: Putty
authors.forename: Gayathri
authors.initials: G
authors.lastname: Srinivasan
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.forename: Charles A
authors.initials: CA
authors.lastname: Parkos
authors.forename: Periasamy
authors.initials: P
authors.lastname: Selvaraj
authors.forename: Matam
authors.initials: M
authors.lastname: Vijay-Kumar
mesh_terms: D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D003872:Dermatitis / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000209:Acute-Phase Proteins; D000936:Antigen-Antibody Complex; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse