Anti-perforin neutralizing antibody reduces myocardial injury in viral myocarditis.
OBJECTIVE
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 0.1 milligrams/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.


CONCLUSIONS
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.
Chun-yan
Guo
G
Cardiology Division, Pediatric Department, Provincal Hospital affiliated to Shandong University, Shandong, Jinan, China.
Bo
Han
H
Hong
Chang
C
Hong-lei
Jiang
J
Xiu-zhen
Han
H
D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D054353:Perforin / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D012333:RNA, Messenger; D054353:Perforin; D053148:Caspase 3