Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40

Copyright © 2015 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 162(2016) vom: 01. Jan., Seite 37-44
1. Verfasser: Wang, Junxiang (VerfasserIn)
Weitere Verfasser: Wang, Lu, Xiang, Ying, Ricklin, Daniel, Lambris, John D, Chen, Gang
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Complement inhibitor Cp40 Nonhuman primate SV40-immortalized porcine aortic endothelial cell Complement C3 Peptides mehr... Pyridones 1-(ethan-1-ol)-2-methyl-3-hydroxypyridin-4-one 30652-21-2
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245 1 0 |a Using an in vitro xenoantibody-mediated complement-dependent cytotoxicity model to evaluate the complement inhibitory activity of the peptidic C3 inhibitor Cp40 
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520 |a 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 
650 4 |a Journal Article 
650 4 |a Research Support, N.I.H., Extramural 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Research Support, U.S. Gov't, Non-P.H.S. 
650 4 |a Complement inhibitor 
650 4 |a Cp40 
650 4 |a Nonhuman primate 
650 4 |a SV40-immortalized porcine aortic endothelial cell 
650 7 |a Complement C3  |2 NLM 
650 7 |a Peptides  |2 NLM 
650 7 |a Pyridones  |2 NLM 
650 7 |a 1-(ethan-1-ol)-2-methyl-3-hydroxypyridin-4-one  |2 NLM 
650 7 |a 30652-21-2  |2 NLM 
700 1 |a Wang, Lu  |e verfasserin  |4 aut 
700 1 |a Xiang, Ying  |e verfasserin  |4 aut 
700 1 |a Ricklin, Daniel  |e verfasserin  |4 aut 
700 1 |a Lambris, John D  |e verfasserin  |4 aut 
700 1 |a Chen, Gang  |e verfasserin  |4 aut 
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