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Lipocalin 2, an innate immune protein, plays a key role in immune‐complex (IC) mediated inflammation
Author(s) -
Aitken Jesse D,
Srinivasan Gayathri,
Sashidhramurthy Rangaiah,
Parkos Charles A,
Selvaraj Periasamy,
Vijay-Kumar Matam
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.55.11
Subject(s) - inflammation , innate immune system , immune system , lipocalin , immunology , arthritis , immune complex , medicine , endocrinology
Lipocalin‐2 (Lcn2), an innate immune protein predominantly secreted by neutrophils, is upregulated by several logs during inflammatory conditions, including autoimmune diseases. However, the defined role of Lcn2 in IC‐mediated inflammation is largely unknown. We investigated the role of Lcn2 in an acute model of IC‐mediated inflammation (Reverse‐Passive Arthus Reaction) and a chronic model of Serum Induced Arthritis (SIA) using Lcn2 knock out (Lcn2KO) and their wild type (WT) littermates. In the acute model of IC‐mediated inflammation, Lcn2KO mice showed approximately 50% reduced inflammation when compared to WT mice. Histopathologic analysis of skin biopsies showed substantially reduced immune cell infiltration at the site of inflammation in Lcn2KO mice. Similarly, neutralization of Lcn2 in WT mice significantly rescued from IC‐mediated inflammation and, further, supplementing rec‐Lcn2 to Lcn2KO mice resulted in inflammation similar to that seen in WT mice. In contrast, in the chronic SIA model, Lcn2KO mice suffered significantly as measured by arthritic disease severity and paw thickness. These results suggest that Lcn2‐dependent immune cell recruitment plays a role in the initiation, perpetuation and, finally, resolution of inflammation. Collectively, our studies demonstrate that targeting Lcn2 may be a promising approach for treating autoimmune diseases.