Differential Role of Lipocalin 2 During Immune Complex–Mediated Acute and Chronic Inflammation in Mice. Issue 4 (28th March 2013)

• Record Type: Journal Article
• Authors: Shashidharamurthy, Rangaiah; Machiah, Deepa; Aitken, Jesse D.; Putty, Kalyani; Srinivasan, Gayathri; Chassaing, Benoit; Parkos, Charles A.; Selvaraj, Periasamy; Vijay‐Kumar, Matam
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 4(2013:Apr.)
• Page Start: 1064
• Page End: 1073
• Publication Date: 2013-03-28
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.37840
• Languages: English
• ISSNs: 0004-3591

Abstract

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. Conclusion: 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.