Suppression of cardiac allograft vasculopathy in mice by inhibition of CC-motif chemokine receptor 5

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• 作者：Chunrong Bao^a ; ¹ ; Zhongwei Lv^b ; ¹ ; Xiaoping Zhang^b ; ¹ ; Jiaquan Zhu^a ; Fangbao Ding^a ; Yunjiao Zhang^a ; Ju Mei^a ; ^{meiju021@126.com}
• 关键词：CCR5 ; CAV ; Heart transplant ; RNAi
• 刊名：Transplant Immunology
• 出版年：2012
• 出版时间：March 2012
• 年：2012
• 卷：26
• 期：2-3
• 页码：128-132
• 全文大小：769 K

文摘

Cardiac allograft vasculopathy (CAV) is the leading cause of late morbidity and mortality in heart-transplant patients. Increasing evidences support the important role of chemokines and their receptors in transplant immunology. Chemokine-chemokine receptor interaction and subsequent recruitment of T-lymphocytes to the graft are early events in the development of chronic rejection of transplanted hearts. In this study, we first inhibited CC-motif chemokine receptor 5 (CCR5) expression by using lentiviral-mediated gene transfer of an anti-CCR5 siRNA, which introduced through CD34⁺ hematopoietic stem/progenitor cell transplantation. Stably marked lymphocytes expressing siRNA and consistent downregulation of CCR5 expression were detected. Our results showed that survival was significantly prolonged in CCR5 knock-down mice and donor hearts from siRNA-treated mice developed markedly less CAV. Infiltration of CD4⁺ and CD8⁺ T-lymphocytes into transplanted hearts was also markedly decreased. These findings suggest that CCR5 plays an important role in CAV development and inhibition of this chemokine could improve long-term survival after cardiac transplantation.