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Absence of the lysosomal protein Limp-2 attenuates renal injury in crescentic glomerulonephritis.

Authors :
Lee, Darren Hiu Kwong
Gan, Poh‐Yi
Katerelos, Marina
Fraser, Scott Andrew
Gleich, Kurt
Holdsworth, Stephen Roger
Power, David Anthony
Source :
Immunology & Cell Biology; May/Jun2014, Vol. 92 Issue 5, p400-408, 9p
Publication Year :
2014

Abstract

In humans, mutations of the Intrinsic lysosomal protein SCARB2 are associated with myoclonic epilepsy, collapsing focal and segmental glomerulosclerosis, and tubular proteinuria. Mice with deficiency of Limp-2 (the murine homologue) develop tubular proteinuria but not focal and segmental glomerulosclerosis and they have a defect in macrophage function. To further elucidate the role of Limp-2 in immune function, we induced anti-glomerular basement membrane (GBM) model of crescentic glomerulonephritis in wild-type (WT) and Limp-2<superscript>-l-</superscript> littermates by intraperitoneal injections of nephrotoxic sheep serum. Renal injury and immune responses were assessed on day 14. Compared with WT, Limp-2<superscript>-l-</superscript> mice had significantly reduced crescent formation, interstitial inflammation and a trend to reduced tubulointerstitial injury. On day 1 during the heterologous phase of the disease, albuminuria was significantly increased in WT but not in Limp-2 <superscript>-l-</superscript> mice. On day 14, albuminuria and renal function were similar in the two groups. There was, however, a significant reduction in the influx of glomerular macrophages and CD4<superscript>+</superscript> T cells in Limp-2 <superscript>-l-</superscript> mice. Interleukin (IL)-4 and macrophage chemoattractant protein-1 (MCP-l) mRNA expression levels were significantly reduced. Despite the reduction in numbers of infiltrating cells, flow cytometry showed no difference in macrophage or T-cell numbers in the peripheral blood from untreated mice. The systemic humoral immune response, determined by glomerular mouse immunoglobulin G (IgG) deposition and mouse anti-sheep IgG subclass production, was similar in both groups. These data suggest that absence of Limp-2 reduces inflammation in experimental crescentic glomerulonephritis with decreased macrophage and T-cell infiltration in the kidney. It suggests an important role for Limp-2 in mediating the inflammatory response. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
08189641
Volume :
92
Issue :
5
Database :
Complementary Index
Journal :
Immunology & Cell Biology
Publication Type :
Academic Journal
Accession number :
96413047
Full Text :
https://doi.org/10.1038/icb.2013.104