Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Accelerated Glomerular Injury in Mer Deficient Mice with Anti-GBM Nephritis
Shao1, Wen-Hai, Zhen1, Yuxuan, Rosenbaum2, Joshua, Eisenberg3, Robert A., McGaha4, Tracy L., Birkenbach1, Mark, Cohen1, Philip L.
The Mer receptor tyrosine kinase plays an important role in clearance of apoptotic cells and in modulation of both innate and adaptive immunity. Mice with the Mer kinase domain deletion (Mer-KO) develop progressive lupus-like autoimmunity. In kidney, Mer expression was shown in the glomeruli with immunofluorescence staining. We thus compared the susceptibility of WT and Mer-KO mice to nephrotoxic anti-glomerular basement membrane-induced murine nephritis.
We induced nephritis in our experimental mice by iv injection of 7.5 ml of nephrotoxic serum per kg mouse body weight. The nephrotoxic serum was raised in sheep against mouse glomerular basement membrane.
Mer-KO but not WT B6 recipients showed increased proteinuria by day 3. Glomeruli from Mer-KO mice were hyperplastic and later became necrotic. PAS-positive staining was evident in Mer-KO capillary spaces as well within tubules, consistent with massive protein leakage. Apoptotic bodies were detectable in the Mer-KO kidney. This early pathological change was associated with a lower survival rate in Mer-KO mice compared to WT. We observed early deposition of mouse anti-sheep IgM antibody on glomeruli from Mer-KO mice but not WT mice. Cytokine profile changes are undergoing investigation.
We discovered a novel protective role of Mer in the development of anti-GBM nephritis. Our data suggest that Mer acts to preserve the kidney from immune-related inflammation.
To cite this abstract, please use the following information:
Shao, Wen-Hai, Zhen, Yuxuan, Rosenbaum, Joshua, Eisenberg, Robert A., McGaha, Tracy L., Birkenbach, Mark, et al; Accelerated Glomerular Injury in Mer Deficient Mice with Anti-GBM Nephritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :150