进行性肾脏疾病中的肥大细胞浸润和趋化因子表达

Mast cell infiltration and chemokine expression in progressive renal disease.

作者信息

Jones Susan E, Kelly Darren J, Cox Alison J, Zhang Yuan, Gow Renae M, Gilbert Richard E

机构信息

University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia.

出版信息

Kidney Int. 2003 Sep;64(3):906-13. doi: 10.1046/j.1523-1755.2003.00183.x.

DOI:10.1046/j.1523-1755.2003.00183.x

PMID:12911540

Abstract

BACKGROUND

Mast cells are growth factor-rich, bone marrow-derived cells that infiltrate injured tissue where they have been implicated in the pathogenesis of progressive fibrosis.

METHODS

Mast cell infiltration and the expression of related chemoattractants was examined following 5/6 nephrectomy, a model of progressive, nonimmune-mediated renal injury. In addition, expression of the profibrotic cytokine, transforming growth factor-beta (TGF-beta) within mast cells and the effects of renoprotective therapy with angiotensin-converting enzyme (ACE) inhibition were also determined.

RESULTS

Renal injury was accompanied by mast cell infiltration, in close proximity to areas of tubulointerstitial fibrosis. Mast cells displayed toluidine blue metachromasia and were immunopositive for TGF-beta1 as well as chymase and tryptase. The expression of several mast cell chemokines, including stem cell factor, interleukin-8 (IL-8), and also TGF-beta1, were increased in 5/6 nephrectomized kidneys. ACE inhibition with ramipril led to a reduction in renal injury in association with attenuation of mast cell infiltration and chemokine expression.

CONCLUSION

Mast cell infiltration and related chemokine expression are prominent and early features following renal mass reduction and may contribute pathogenetically to progressive renal injury.

摘要

背景

肥大细胞是富含生长因子、来源于骨髓的细胞，可浸润受损组织，在进行性纤维化的发病机制中发挥作用。

方法

在5/6肾切除术后（一种进行性、非免疫介导的肾损伤模型），检测肥大细胞浸润及相关趋化因子的表达。此外，还测定了肥大细胞内促纤维化细胞因子转化生长因子-β（TGF-β）的表达以及血管紧张素转换酶（ACE）抑制的肾脏保护治疗效果。

结果

肾损伤伴有肥大细胞浸润，紧邻肾小管间质纤维化区域。肥大细胞显示甲苯胺蓝异染性，对TGF-β1、糜蛋白酶和组织蛋白酶呈免疫阳性。在5/6肾切除的肾脏中，几种肥大细胞趋化因子的表达增加，包括干细胞因子、白细胞介素-8（IL-8）以及TGF-β1。用雷米普利抑制ACE可减轻肾损伤，同时减少肥大细胞浸润和趋化因子表达。