Immunological rejection of heart transplant: how lytic granules from cytotoxic T lymphocytes damage guinea pig ventricular myocytes

Pflügers Archiv - Tập 420 - Trang 172-179 - 1992
Ofer Binah1, Shimon Marom2, Irit Rubinstein2, Richard B. Robinson1, Gideon Berke3, Brian F. Hoffman1
1Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, USA
2Rappaport Family Institute, Department of Physiology and Biophysics, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel
3Department of Cell Biology, The Weizmann Institute, Rehovot, Israel

Tóm tắt

We investigated the mechanism by which lytic granules extracted from cytotoxic T lymphocytes (CTL) damage guinea pig ventricular myocytes in order to dertermine whether their actions can be related to the overall immunological rejection of the transplanted heart. Granule-induced myocyte morphological changes and final destruction were preceded by shortening of action potential duration (APD) and reductions of the resting potential and the action potential amplitude. APD shortening was probably caused by a granule-induced increase in outward current (most likely non-specific). Ryanodine, which blocks Ca2+ release from the sacroplasmic reticulum, did not interfere with the morphological and electrophysiological effects of lytic granules. Fura-2 imaging indicated that [Ca2+]i initially increased about 2-fold from 90.0±11.5 nM, while cell length decreased less than 5% from a mean value of 99.0±9.0 μm. A further increase in [Ca2+]i (>10 fold) was associated with progressive contracture and destruction, suggesting that the structural damage inflicted by lytic granules is caused by [Ca2+]i overload. The results indicate that the cytocidal action of CTL-derived lytic granules may be involved in immunologically induced damage, even to the extent of rejection of the transplanted heart.

Tài liệu tham khảo

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