Lipocalin-2 is involved in immune-complex mediated inflammation (102.23)

Abstract

Abstract Lipocalin-2 (Lcn-2) is an innate immune protein whose expression is upregulated by several orders of magnitude in response to inflammation/injury/infection by variety of cells including neutrophils. However, the role of Lcn-2 induction in IC-induced inflammation is largely unknown. Here in, we have investigated the role of Lcn-2 during IC-mediated inflammation using Lcn-2 knock out (Lcn-2KO) and wild type (WT) mice. IC-mediated inflammation upregulated systemic Lcn-2 in WT mice when compared to naïve mice. The neutrophil chemoattractant KC was significantly elevated in WT, but not in Lcn-2KO mice, in response to IC-induced inflammation. Consistently Lcn-2KO mice showed about 50% reduced IC-mediated inflammation when compared to WT mice. Histopathological analysis of skin biopsy showed reduced inflammatory cell infiltration at inflamed site in Lcn-2KO mice relative to WT mice. Administration of recLcn-2 into Lcn-2KO mice resulted in inflammation similar to that of WT mice in response to IC. Lastly, we observed that neutralization of Lcn-2 via neutralizing mAb significantly reduced inflammation in WT mice. These results suggest that engagement of FcγRs expressed on local inflammatory cells with ICs leads to the induction of Lcn-2. Such IC-induced Lcn-2 expression may be essential for infiltration inflammatory cells at the site of inflammation. Our studies show that therapeutic targeting of Lcn-2 may be useful approach for treating IC-mediated inflammatory/autoimmune diseases