Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40
Simple and reliable methods for evaluating the inhibitory effects of drug candidates on complement activation are essential for preclinical development. Here, using an immortalized porcine aortic endothelial cell line (iPEC) as target, we evaluated the feasibility and effectiveness of an in vitro xenoantibody-mediated complement-dependent cytotoxicity (CDC) model for evaluating the complement inhibitory activity of Cp40, a potent analog of the peptidic C3 inhibitor compstatin. The binding of human xenoantibodies to iPECs led to serum dilution-dependent cell death. Pretreatment of the human serum with Cp40 almost completely inhibited the deposition of C3 fragments and C5b-9 on the cells, resulting in a dose-dependent inhibition of CDC against the iPECs. Using the same method to compare the effects of Cp40 on complement activation in humans, rhesus and cynomolgus monkeys, we found that the inhibitory patterns were similar overall. Thus, the in vitro xenoantibody-mediated CDC assay may have considerable potential for future clinical use. (C) 2015 Elsevier Inc. All rights reserved.
基金：
National High-Tech Researching and Developing Program (Program 863) of the Ministry of Science and Technology of the People's Republic of ChinaNational High Technology Research and Development Program of China [2012AA021010]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81172825]; U.S. National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AI069730, AI030040]; National Science FoundationNational Science Foundation (NSF) [1423304]; European CommunityEuropean Commission [602699]; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [N01AI030040, P01AI068730, R01AI030040, R13AI069730] Funding Source: NIH RePORTER; Division of Computing and Communication FoundationsNational Science Foundation (NSF)NSF - Directorate for Computer & Information Science & Engineering (CISE) [1423304] Funding Source: National Science Foundation
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Inst Organ Transplantat, Tongji Hosp, Wuhan 430030, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
wang junxiang,wang lu,xiang ying,et al.Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40[J].CLINICAL IMMUNOLOGY.2016,162:37-44.doi:10.1016/j.clim.2015.11.002.
APA：
wang,junxiang,wang,lu,xiang,ying,ricklin,daniel,lambris,john d.&chen,gang.(2016).Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40.CLINICAL IMMUNOLOGY,162,
MLA：
wang,junxiang,et al."Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40".CLINICAL IMMUNOLOGY 162.(2016):37-44
