a protective role of mer receptor tyrosine kinase in nephrotoxic serum-induced nephritis：一个在肾毒血清性肾炎mer受体酪氨酸激酶的保护作用.pdfVIP

Clinical Immunology (2010) 136, 236–244 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m C l i n i c a l I m m u n o l o g y w w w . e l s e v i e r . c o m / l o c a t e / y c l i m A protective role of Mer receptor tyrosine kinase in nephrotoxic serum-induced nephritis Wen-Hai Shao a , Yuxuan Zhen a , Joshua Rosenbaum b , Robert A. Eisenberg b , Tracy L. McGaha c , Mark Birkenbach a , Philip L. Cohen a,⁎ a Department of Medicine, Section of Rheumatology, Temple University, Philadelphia, PA 19140, USA b Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA 19104, USA c Immunotherapy Center, Department of Medicine, Medical College of Georgia, Augusta, GA 30912, USA Received 18 January 2010; accepted with revision 1 April 2010 Available online 4 May 2010 KEYWORDS Abstract The Mer receptor tyrosine kinase is strongly expressed in the glomerulus. We MerTK; wondered if this molecule might modify immune-mediated glomerular disease through its Glomerulonephritis; functions as a receptor for apoptotic cells and immunoregulatory molecule. Mer-knockout (KO) Apoptotic clearance; mice showed decreased survival rate and greatly increased proteinuria and serum urea levels Cytokine regulation 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-tre