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

来源：

KIDNEY INTERNATIONAL | 2011年 / 80卷 / 09期

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

页码：946 / 958

页数：13

共 42 条

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