Bone marrow transplantation attenuates murine IgA nephropathy: Role of a stem cell disorder

被引:59
作者
Imasawa, T
Nagasawa, R
Utsunomiya, Y
Kawamura, T
Zhong, Y
Makita, N
Muso, E
Miyawaki, S
Maruyama, N
Hosoya, T
Sakai, O
Ohno, T
机构
[1] Jikei Univ, Sch Med, Dept Microbiol, Minato Ku, Tokyo 1058461, Japan
[2] Jikei Univ, Sch Med, Dept Internal Med, Minato Ku, Tokyo 1058461, Japan
[3] Saitama Med Sch, Ctr Med, Div Hemodialysis, Moroyama, Saitama, Japan
[4] Kyoto Univ, Dept Internal Med, Kyoto 606, Japan
[5] Nippon Shinyaku Co Ltd, Res Labs, Kyoto 601, Japan
[6] Tokyo Metropolitan Inst Gerontol, Dept Mol Pathol, Tokyo, Japan
关键词
hematopoietic stem cells; glomerulonephritis; immunoglobulin A; transplantion immunology;
D O I
10.1046/j.1523-1755.1999.00750.x
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
Background. The pathogenesis of IgA nephropathy is still obscure. The aim of this study was to investigate whether the fundamental pathogenesis of IgA nephropathy lies in bone marrow stem cells (BMCs). Methods. We used donors of two different strains for bone marrow transplantation (BMT) into mice with a high content of serum IgA (ddY strain, HIGA mice), a murine model of IgA nephropathy. One group (B6-->HIGA, N = 5) received BMCs of C57BL/6j (B6) mice, and the other (HIGA-->HIGA, N = 8) were reconstituted with BMCs of HIGA mice. Results. Twenty-six weeks after BMT, in B6-->HIGA mice, mesangial deposits of IgA and C3 were statistically milder than those in HIGA-->HIGA mice. Light microscopic observations disclosed that glomerular sclerosis and mesangial matrix expansion in B6-->HIGA mice were decreased compared with those in HIGA-->HIGA mice. These B6-->HIGA mice also excreted less urinary albumin than HIGA-->HIGA mice. Furthermore, serum levels of IgA in B6-->HIGA mice were markedly lower than those in HIGA-->HIGA mice. Size analysis of serum IgA revealed that macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. Conclusions. Our results suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells, and that BMT from normal donors can attenuate glomerular lesions in HIGA mice. This approach may offer a new avenue to study the pathogenesis of IgA nephropathy.
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收藏
页码:1809 / 1817
页数:9
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