title: Prognosis of sepsis induced by cecal ligation and puncture in mice improved by anti-Clonorchis Sinensis cyclopholin a antibodies.
abstract: BACKGROUND
  Cyclophilin A (CyPA), a ubiquitously distributed intracellular protein, is thought to be one of the important inflammatory factors and plays a significant role in the development process of sepsis. In the form of cytokine, CyPA deteriorates sepsis by promoting intercellular communication, apoptosis of endothelial cells and chemotactic effect on inflammatory cells. In our previous study, cyclophilin A of Clonorchis sinensis (CsCyPA), a type of excretory-secretory antigen, could induce the patients infected with Clonorchis sinensis to produce specific anti-CsCyPA antibodies. In this study, we investigated whether anti-CsCyPA antibodies could cross-react with CyPA and then play a protective role against sepsis, just like other anti-cytokine antagonists.
  
  
  METHODS
  The mice model with sepsis was established with cecal ligation and puncture (CLP). Fifty mg/kg purified anti-CsCyPA antibodies were injected via the caudal vein 6 h after the CLP operation, and persistent observation was performed for 72 h. Blood samples and tissues were collected at 6 h, 12 h, 24 h, 48 h and 72 h after CLP. Cytokines in serum were measured by ELISA. Lung and mesentery tissues were stained with hematoxylin-eosin. Endothelial cells (ECs) isolated from murine aorta were co-cultured with CyPA of mice (MuCyPA) and anti-CsCyPAs for 24 h, then, viability was measured by Cell Counting Kit-8.
  
  
  RESULTS
  Anti-CsCyPA antibodies could combine with MuCyPA and inhibit its peptidyl prolyl isomerase (PPIase) activity. In the antibodies treatment group, blood coagulation indicators including PT, aPTT, D-dimer and platelet count were obviously more ameliorative, the proinflammary factors like IL-6, TNF-α, IL-1β were significantly lower at 12 h and 24 h after surgery and the viability of ECs was significantly improved compared to those in the control group. Furthermore, the survival rate was elevated, ranging from 10.0 % to 45.0 % compared to the control group.
  
  
  CONCLUSIONS
  These antibodies may have a favorable effect on sepsis via inhibition of enzymic activity or protection of endothelial cells.
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. songtianzhang@163.com.|Education Ministry Key Laboratory for Tropical Disease Control Research, Sun Yat-sen University, Guangzhou, Guangdong, China. songtianzhang@163.com.
authors.forename: Tianzhang
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. 290224840@qq.com.|Education Ministry Key Laboratory for Tropical Disease Control Research, Sun Yat-sen University, Guangzhou, Guangdong, China. 290224840@qq.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. 121863540@qq.com.|Education Ministry Key Laboratory for Tropical Disease Control Research, Sun Yat-sen University, Guangzhou, Guangdong, China. 121863540@qq.com.
authors.forename: Jintao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. 921295597@qq.com.
authors.forename: Lilin
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. 13207468482@163.com.|Education Ministry Key Laboratory for Tropical Disease Control Research, Sun Yat-sen University, Guangzhou, Guangdong, China. 13207468482@163.com.
authors.forename: Hongling
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. 378849150@qq.com.
authors.forename: Tailong
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. hhuaiqiu@medmail.com.cn.
authors.forename: Huaiqiu
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. huxuchu@mail.sysu.edu.cn.|Education Ministry Key Laboratory for Tropical Disease Control Research, Sun Yat-sen University, Guangzhou, Guangdong, China. huxuchu@mail.sysu.edu.cn.
authors.forename: Xuchu
authors.initials: X
authors.lastname: Hu
mesh_terms: D000818:Animals; D002432:Cecum / Q000473:pathology*; D003004:Clonorchis sinensis; D021983:Cyclophilins / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015801:Helminth Proteins / Q000494:pharmacology*; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D029701:Saccharomyces cerevisiae Proteins; D018805:Sepsis / Q000188:drug therapy*
chemical_list: C438144:ASI1 protein, S cerevisiae; D016207:Cytokines; D015801:Helminth Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D021983:Cyclophilins