Reduction of viral myocarditis in mice lacking perforin.
Cellular immunity plays an important role and contributes to morbidity and mortality in the development of cardiomyopathy secondary to acute myocarditis. Lymphocytotoxicity has been proposed as due to infiltrated cytotoxic T lymphocytes (CTLs). Perforin is thought to be a major factor responsible for the cytolytic properties of the CTLs. To investigate whether mice lacking perforin have enhanced severity of viral myocarditis and acceleration of myocardial apoptosis, perforin knockout (KO) mice were infected with encephalomyocarditis virus. The average cardiac viral titer in perforin KO mice was not significantly different from that in the wild type mice. The heart weight/body weight ratio in perforin KO mice on days 4 and 12 were the same in the wild type mice (n=4 of each). Hearts in perforin KO mice were smaller than that in perforin + mice and grades of myocardial necrosis and lymphocyte infiltration were significantly reduced than in perforin + mice on day 12 after viral inoculation. In the perforin KO mice, the number of apoptotic cells was significantly higher than in wild type on day 4. Perforin blockade induced the early induction of myocardial apoptosis and suppressed the late onset of myocardial injury by cellular autoimmunity. Blockade of perforin gene expression at an early stage may limit viral myocarditis for therapeutic intervention.
Koike
H
H
Department of Laboratory Medicine, Gunma University School of Medicine, Maebashi, Japan. ZVT03554@nifty.com
Kanda
T
T
Sumino
H
H
Yokoyama
T
T
Arai
M
M
Motooka
M
M
Suzuki
T
T
Tamura
J
J
Kobayashi
I
I
D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D004686:Encephalomyocarditis virus / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000276:immunology / Q000473:pathology / Q000821:virology*; D009929:Organ Size; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin