Macrophages are essential contributors to kidney injury in murine cryoglobulinemic membranoproliferative glomerulonephritis

被引:36
作者
Guo, Shunhua [1 ]
Wietecha, Tomasz A. [1 ]
Hudkins, Kelly L. [1 ]
Kida, Yujiro [2 ]
Spencer, Min W. [1 ]
Pichaiwong, Warangkana [1 ]
Kojima, Ichiro [1 ]
Duffield, Jeremy S. [2 ]
Alpers, Charles E. [1 ]
机构
[1] Univ Washington, Dept Pathol, Seattle, WA 98195 USA
[2] Univ Washington, Div Nephrol, Dept Med, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
macrophages; membranoproliferative glomerulonephritis; pathophysiology of renal disease and progression; LYMPHOPOIETIN TRANSGENIC MICE; CRESCENTIC GLOMERULONEPHRITIS; TGF-BETA; RECEPTOR; ACTIVATION; EXPRESSION; REPAIR; CELLS; MECHANISMS; PROTECTION;
D O I
10.1038/ki.2011.249
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Mice transgenic for thymic stromal lymphopoietin (TSLP), under regulation of the lymphocyte-specific promoter Lck, develop cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN) similar to the disease in patients. To determine whether infiltrating macrophages, a hallmark of this disease, are deleterious or beneficial in the injury process, we developed Lck-TSLP transgenic mice expressing the human diphtheria toxin receptor (DTR) under control of the monocyte/macrophage-restricted CD11b promoter (Lck-TSLP; CD11b-DTR). Treatment with DT resulted in a marked reduction of monocytes/macrophages in the peritoneal cavity of both CD11b-DTR and Lck-TSLP; CD11b-DTR mice and marked reduction of macrophage infiltration in glomeruli of Lck-TSLP; CD11b-DTR mice. Lck-TSLP; CD11b-DTR mice, with or without toxin treatment, had similar levels of cryoglobulinemia and glomerular immunoglobulin deposition as Lck-TSLP mice. Lck-TSLP; CD11b-DTR mice, treated with toxin, had reduced mesangial matrix expansion, glomerular collagen IV accumulation, expression of the activation marker alpha-smooth muscle actin and transforming growth factor-beta 1 in mesangial cells, and proteinuria compared with control mice. Thus, macrophage ablation confers protection in this model and indicates a predominately deleterious role for macrophages in the progression of kidney injury in cryoglobulinemic MPGN. Kidney International (2011) 80, 946-958; doi:10.1038/ki. 2011.249; published online 3 August 2011
引用
收藏
页码:946 / 958
页数:13
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