Back to Search
Start Over
Physiological changes induced in cardiac myocytes by cytotoxic lymphocytes: an autoimmune model.
- Source :
-
Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 1994 Mar; Vol. 26 (3), pp. 351-60. - Publication Year :
- 1994
-
Abstract
- Background: cytotoxic lymphocytes are important in the pathogenesis of several disease states, yet, the pathophysiology of lymphocyte-myocyte interaction is not well known.<br />Methods and Results: We have developed a model for the in vitro evaluation of autoimmune cytotoxic myocardial damage. Cardiac myocytes were repeatedly injected to adult autologous rats. Following 3 months, histological evidence of myocarditis was seen in 20% of the hearts. Cultured myocytes obtained from newborn rats were exposed to lymphocytes isolated from the immunized animals. Cytotoxic activity was measured using crystal violet staining test. The percentage of killing was increased as the ratio of lymphocytes/myocytes was increased. Verapamil did not block this cytotoxic effect. No killing was seen when myocytes were exposed to non-sensitized lymphocytes. Physiological changes induced in myocytes by cytotoxic lymphocytes were studied. Cell wall motion was measured by an optical method and action potentials with intracellular microelectrodes. Physiological changes observed in myocytes following exposure to cytotoxic lymphocytes included: Impaired relaxation with prolonged contractions, oscillations and prolongation of the plateau of the action potential. Cellular contraction was prolonged up to 4 s before total arrest of spontaneous activity. Verapamil but not tetrodotoxin restored action potentials and contractions to normal. Supernatant collected from cultures of myocytes and lymphocytes had the same effect on myocytes contractility as observed following exposure of myocytes to cytotoxic lymphocytes.<br />Conclusions: This supports our hypothesis that these physiological alterations observed in myocytes are mediated by a soluble factor secreted by cytotoxic lymphocytes.
- Subjects :
- Action Potentials drug effects
Animals
Autoimmune Diseases immunology
Cell Transplantation
Cells, Cultured
Cytotoxicity, Immunologic
Immunization
Male
Models, Biological
Myocardial Contraction drug effects
Myocarditis immunology
Rats
Single-Blind Method
T-Lymphocytes, Cytotoxic metabolism
Tetrodotoxin pharmacology
Verapamil pharmacology
Autoimmune Diseases pathology
Myocarditis pathology
Myocardium cytology
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2828
- Volume :
- 26
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of molecular and cellular cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 8028018
- Full Text :
- https://doi.org/10.1006/jmcc.1994.1044