The complement C5b-9 complexes induced injury of glomerular mesangial cells in rats with Thy-1 nephritis by increasing nitric oxide synthesis |
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Authors: | Wang Yingwei He Qiuzhao Qin Huilian Xu Jinghua Tong Jianxia Gao Lingjuan Xu Juan |
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Affiliation: | Department of Immunology, Nanjing Medical University, Nanjing Hanzhong Road 140 #, Jiangsu Province, 210029, PR China. wangyw@njmu.edu.cn |
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Abstract: | Thy-1 nephritis (Thy-1 N), namely, anti-Thy-1 or anti-thymocyte serum (ATS) induced nephritis (ATSN), is a typical model of human mesangioproliferative glomerulonephritis. The pathologic changes of glomerular mesangial cells (GMCs) in Thy-1 N are complement-dependent, especially C5b-9 complexes, but the role of C5b-9 in the mechanism of Thy-1 N has not been defined. Because previous studies have demonstrated that sublytic C5b-9 can increase production of several inflammatory mediators from resident glomerular cells, we utilized the isolated human membrane-bound C5b-9 complexes to stimulate the cultured rat GMCs and examined whether the GMCs can also induce the synthesis of nitric oxide (NO) in vitro. Simultaneously, the effects of antiserum against rat C5b-9 and NG-monomethyl-L-arginine (L-NMMA, NO inhibitor), including interfering with the formation of C5b-9, reducing NO production and GMCs injury were observed. The results showed that sublytic C5b-9 can increase synthesis of inducible NO from the stimulated GMCs, and that the anti-C5b-9 antiserum can obviously inhibit the pathologic changes in Thy-1 N, while L-NMMA can decrease the GMCs damage although the effect is not so significant as that of the anti-C5b-9 antiserum. These findings indicate that the synthesis of NO by GMCs can be promoted by sublytic C5b-9, and that lesions of GMCs in rats with Thy-1 N are prevented by either inhibiting C5b-9 formation or NO elevation in advance. The pathologic changes of GMCs in Thy-1 N are indeed complement C5b-9-dependent, and the glomerular injury can be mediated in part through elevation of NO from the GMCs after the sublytic C5b-9 stimulation. |
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Keywords: | Thy-1 nephritis Mesangioproliferative glomerulonephritis Glomerular mesangial cells C5b-9 complexes Nitric oxide Antiserum against C5b-9 NG-monomethyl- smallcaps" >l-arginine |
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