Apoptosis in a canine model of acute Chagasic myocarditis.
Histologic, ultrastructural and nick end labeling studies were made to evaluate the occurrence of apoptosis in the hearts of dogs with acute myocarditis due to experimental infection with T. cruzi. The best results for the detection of apoptosis by nick end labeling were obtained by a method combining the use of terminal deoxynucleotidyl transferase, CoCl2 and fluorescein-conjugated deoxyuridine triphosphate, followed by counterstaining of DNA with 4'6-diamidino-2-phenylindole (DAPI) and examination by laser scanning confocal fluorescence microscopy. Apoptosis was found in: (1) cardiac myocytes; (2) endothelial cells of capillaries and venules: (3) immune effector cells, including macrophages, interstitial dendritic cells (antigen-presenting cells) and granular and agranular lymphocytes, and (4) intra- and extracellular forms of T. cruzi. The apoptosis in myocytes and endothelial cells affected cells that were not infected by T. cruzi and was probably caused by the release of toxic mediators of inflammation. The apoptosis of immune effector cells could be related either to the subsidence of inflammation or to modulation (and even failure) of the immune response. The finding of apoptosis in T. cruzi confirms the results of other studies showing that this phenomenon occurs during the differentiation of trypomastigotes in vitro. Thus, apoptosis constitutes an important and multifactorial event in the pathogenesis of acute Chagasic myocarditis.
Zhang
J
J
Pathology Section, National Heart, Lung & Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Andrade
Z A
ZA
Yu
Z X
ZX
Andrade
S G
SG
Takeda
K
K
Sadirgursky
M
M
Ferrans
V J
VJ
D000818:Animals; D017209:Apoptosis; D002598:Chagas Cardiomyopathy / Q000473:pathology*; D053938:DNA Fragmentation; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure; D020287:In Situ Nick-End Labeling / Q000379:methods; D008214:Lymphocytes / Q000378:metabolism / Q000648:ultrastructure; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D014349:Trypanosoma cruzi / Q000648:ultrastructure