| 저자(한글) |
Ponce, Nicol #x00E1,s Eric,Sanmarco, Liliana Maria,Eberhardt, Natalia,Garc #x00ED,a, M #x00F3,nica Cristina,Rivarola, H #x00E9,ctor Walter,Cano, Roxana Carolina,Aoki, Maria Pilar |
| 저자(영문) |
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| 소속기관 |
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| 소속기관(영문) |
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| 출판인 |
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| 간행물 번호 |
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| 발행연도 |
2016-01-01 |
| 초록 |
Increasing evidence demonstrates that generation of extracellular adenosine from ATP, which is hydrolyzed by the CD39/CD73 enzyme pair, attenuates the inflammatory response and deactivates macrophage antimicrobial mechanisms. Although CD73 is emerging as a critical pathway and therapeutic target in cardiovascular disorders, the involvement of this ectonucleotidase during myocardial infection has not been explored. Using a murine model of infection with Trypanosoma cruzi , the causal agent of Chagas cardiomyopathy, we observed a sudden switch from the classical M1 macrophage (microbicidal) phenotype toward an alternative M2 (repairing/anti-inflammatory) phenotype that occurred within the myocardium very shortly after BALB/c mice infection. The observed shift in M1/M2 rate correlated with the cardiac cytokine milieu. Considering that parasite persistence within myocardium is a necessary and sufficient condition for the development of the chronic myocarditis, we hypothesized that CD73 activity may counteract cardiac macrophage microbicidal polarization, rendering the local immune response less effective. In fact, a transient treatment with a specific CD73 inhibitor (adenosine 5 #x2032;- #x03B1;, #x03B2;-methylene-diphosphate) enhanced the microbicidal M1 subset predominance, diminished IL-4 #x2013; and IL-10 #x2013;producing CD4 + T cells, promoted a proinflammatory cytokine milieu, and reduced parasite load within the myocardium during the acute phase. As a direct consequence of these events, there was a reduction in serum levels of creatine kinase muscle #x2013;brain isoenzyme, a myocardial-specific injury marker, and an improvement in the electrocardiographic characteristics during the chronic phase. Our results demonstrate that this purinergic system drives the myocardial immune response postinfection and harbors a promising potential as a therapeutic target. |
| 원문URL |
http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=03553784&target=NART&cn=NART76032180 |
| 첨부파일 |
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