Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia.
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| Abstract |
With increased industrial development, cadmium is an increasingly important environmental pollutant. Studies have identified various adverse effects of cadmium on human beings. However, the relationships between cadmium pollution and the pathogenesis of preeclampsia remain elusive. The objective of this study is to explore the effects of cadmium on immune system among preeclamptic patients and rats. The results showed that the cadmium levels in the peripheral blood of preeclamptic patients were significantly higher than those observed in normal pregnancy. Based on it, a novel rat model of preeclampsia was established by the intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg body weight) on gestational days 9-14. Key features of preeclampsia, including hypertension, proteinuria, placental abnormalities and small foetal size, appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies (AT1-AA), by increasing the expression of activation-induced cytosine deaminase (AID) in B cells. AID is critical for the maturation of antibody and autoantibody responses. In addition, angiotensin II type 1-receptor-agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, was responsible for the deposition of complement component 5 (C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R) activation. C5a is a fragment of C5 that is released during C5 activation. Selectively interfering with C5a signalling by a complement C5a receptor-specific antagonist significantly attenuated hypertension and proteinuria in Cd-injected pregnant rats. Our results suggest that cadmium induces immune abnormalities that may be a key pathogenic contributor to preeclampsia and provide new insights into treatment strategies of preeclampsia.
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| Authors | Qiong Zhang, Yinping Huang, Keke Zhang, Yanjun Huang, Yan Yan, Fan Wang, Jie Wu, Xiao Wang, Zhangye Xu, Yongtao Chen, Xue Cheng, Yong Li, Jinyu Jiao, Duyun Ye |
| Journal | Environmental pollution (Barking, Essex : 1987) (Environ Pollut) Vol. 218 Pg. 770-782 (Nov 2016) ISSN: 1873-6424 [Electronic] England |
| PMID | 27511439 (Publication Type: Journal Article) |
| Copyright | Copyright © 2016 Elsevier Ltd. All rights reserved. |
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