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Anti-perforin neutralizing antibody reduces myocardial injury in viral myocarditis

Published online by Cambridge University Press:  14 October 2009

Guo Chun-yan ,
Han Bo ,
Chang Hong ,
Jiang Hong-lei  and
Han Xiu-zhen
Guo Chun-yan
Affiliation:
Cardiology Division, Pediatric Department, Provincal Hospital Affiliated to Shandong University, Shandong, Jinan, China
Han Bo*
Affiliation:
Cardiology Division, Pediatric Department, Provincal Hospital Affiliated to Shandong University, Shandong, Jinan, China
Chang Hong
Affiliation:
Pediatric Department, The Hospital Affiliated to Qingdao University, Shandong, Qingdao, China
Jiang Hong-lei
Affiliation:
Cardiology Division, Pediatric Department, Provincal Hospital Affiliated to Shandong University, Shandong, Jinan, China
Han Xiu-zhen
Affiliation:
Cardiology Division, Pediatric Department, Provincal Hospital Affiliated to Shandong University, Shandong, Jinan, China
*
Correspondence to: Han Bo, Pediatric Devision, Pediatric Department, Provincial Hospital Affiliated to Shandong University, Shandong, Jinan, China. Postal code: 250021; Tel: +86 531 86867000; Fax: +86 531 87917741; E-mail: hanbo45@126.com
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Abstract

Aim

To investigate the role of anti-perforin neutralizing antibody in viral myocarditis.

Methods

We divided 45 Balb/c mice randomly into 3 groups, a normal control group, a control group inoculated with coxsackie virus B3, and a group inoculated with anti-perforin neutralizing antibody. The second group was inoculated with 0.15 milliliters coxsackie virus B3, and the third group additionally with 0.1milligrams/kilogram anti-perforin neutralizing antibody at time points of 6 hours and 3 days after infection. Histopathology was performed using haematoxylin and eosin, with apoptosis examined by the terminal transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick, end-labeling method, or Tunel. The expression of caspase-3 in myocardium was investigated by immunohistochemistry and reverse-transcription polymerase chain reaction.

Results

The pathologic score, myocardial viral titers, average percentages of apoptotic cardiomyocytes, expression of active caspase-3 protein and messenger ribonucleic acid in the myocardium of the mice receiving anti-PFP neutralizing antibody therapy were all significantly reduced when compared to values from the group inoculated with coxsackie virus B3. The rates of expression of Caspase-3 and myocardial apoptosis were positively correlated with the scores for myocardial pathology.

Conclusion

Our results suggest that anti- perforin neutralizing antibody can reduce the myocardial damage by blocking the perforin/granzyme pathway, and downregulating the expression of messenger ribonucleic acid and protein of Caspase-3. These approaches may offer promising novel therapeutic strategies for the clinical treatment of viral myocarditis.

Keywords

Micecytotoxic T lymphocytesApoptosisCaspase-3
Type
Original Articles
Information
Cardiology in the Young , Volume 19 , Issue 6 , December 2009 , pp. 601 - 607
Copyright
Copyright © Cambridge University Press 2009

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