A protective role of Mer receptor tyrosine kinase in nephrotoxic serum-induced nephritis.
The Mer receptor tyrosine kinase is strongly expressed in the glomerulus. We wondered if this molecule might modify immune-mediated glomerular disease through its functions as a receptor for apoptotic cells and immunoregulatory molecule. Mer-knockout (KO) mice showed decreased survival rate and greatly increased proteinuria and serum urea levels compared to wild type (WT) mice by day 3 after injection of NTS. Their glomeruli were hyperplastic and later became necrotic. In the glomerulus of WT mice, a significant increase of Mer expression was observed. Apoptotic bodies were evident in NTS-treated Mer-KO kidneys, but not in normal controls. NTS-treated Mer-KO mice had massive neutrophil infiltration and inflammatory cytokine expression. Mer thus has a critical role in attenuating renal inflammation, both as a receptor for apoptotic cells and as a molecule that downregulates inflammation.
Shao
Wen-Hai
WH
Department of Medicine, Temple University, Philadelphia, PA 19140, USA.
Zhen
Yuxuan
Y
Rosenbaum
Joshua
J
Eisenberg
Robert A
RA
McGaha
Tracy L
TL
Birkenbach
Mark
M
Cohen
Philip L
PL
D000818:Animals; D017209:Apoptosis; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D007106:Immune Sera / Q000633:toxicity; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009393:Nephritis / Q000201:enzymology* / Q000276:immunology*; D009504:Neutrophils; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000076202:c-Mer Tyrosine Kinase
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D007106:Immune Sera; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase
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