ENDOTHELIAL-CELLS AS CYTOTOXIC EFFECTOR-CELLS - CYTOKINE-ACTIVATED RAT ISLET ENDOTHELIAL-CELLS LYSE SYNGENEIC ISLET CELLS VIA NITRIC-OXIDE

Citation
L. Steiner et al., ENDOTHELIAL-CELLS AS CYTOTOXIC EFFECTOR-CELLS - CYTOKINE-ACTIVATED RAT ISLET ENDOTHELIAL-CELLS LYSE SYNGENEIC ISLET CELLS VIA NITRIC-OXIDE, Diabetologia, 40(2), 1997, pp. 150-155
Citations number
31
Categorie Soggetti
Endocrynology & Metabolism
Journal title
ISSN journal
0012186X
Volume
40
Issue
2
Year of publication
1997
Pages
150 - 155
Database
ISI
SICI code
0012-186X(1997)40:2<150:EACE-C>2.0.ZU;2-Y
Abstract
In vivo, each beta cell is located in proximity to at least one capill ary islet endothelial cell. Rat aorta and islet endothelial cells can be activated in vitro to express inducible nitric oxide synthase by a cytokine mixture of tumour necrosis factor-alpha, gamma-interferon, an d interleukin-1 beta and to produce high concentrations of nitric oxid e. We have performed co-culture experiments with rat islet endothelial cells together with isolated syngeneic islet cells at low target:effe ctor ratios with or without previous cytokine challenge of endothelial cultures. Co-cultures were always free of exogenous cytokines, which were removed prior to addition of islet cells. We found that pre-activ ated, in contrast to resident islet endothelial cells, at a target:eff ector ratio as low as 1:1 almost completely lysed syngeneic beta and n on-beta cells within 24 h of co-culture. Lysis by pre-activated islet endothelial cells was found to be preceded by DNA damage found in 46% of islet cells after 8 h of co-culture with pre-activated vs 7% with r esting islet endothelial cells. Lysis was blocked to control levels in the presence of the nitric oxide synthase inhibitor N-G-methyl-L-argi nine. With the results presented here, we demonstrate for the first ti me, that activated endothelial lining cells can express effector cell activity and thus can contribute to local tissue destruction, especial ly in organs that are densely capillarized such as pancreatic islets.