ISSN:
1432-0428
Keywords:
Keywords Cytotoxicity
;
diabetes mellitus
;
endothelia
;
nitric oxide.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary In vivo, each beta cell is located in proximity to at least one capillary 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-α, gamma-interferon, and interleukin-1β and to produce high concentrations of nitric oxide. We have performed co-culture experiments with rat islet endothelial cells together with isolated syngeneic islet cells at low target : effector 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-activated, in contrast to resident islet endothelial cells, at a target : effector ratio as low as 1 : 1 almost completely lysed syngeneic beta and non-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 resting islet endothelial cells. Lysis was blocked to control levels in the presence of the nitric oxide synthase inhibitor NG-methyl-L-arginine. With the results presented here, we demonstrate for the first time, that activated endothelial lining cells can express effector cell activity and thus can contribute to local tissue destruction, especially in organs that are densely capillarized such as pancreatic islets. [Diabetologia (1997) 40: 150–155]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s001250050656
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