Activated macrophages kill pancreatic syngeneic islet cells via arginine-dependent nitric oxide generation.

Abstract:

:IL-1 and TNF alpha are assumed to be major mediators of islet cell destruction during the pathogenesis of type 1 diabetes. Here we show by neutralization of the two cytokines with excess antibody that IL-1 and TNF alpha do not contribute to the cytotoxic activity of activated macrophages towards isolated islet cells. However, islet cells can be protected from lysis by depleting the culture medium of L-arginine or by adding the antagonist NG-monomethyl-L-arginine, both of which inhibit the generation of nitric oxide by activated macrophages. These results indicate a role of nitric oxide or its equivalent, the endothelium-derived relaxing factor in the development of type 1 diabetes. This is the first report showing that nitric oxide may damage normal cells and thus may be a hitherto unrecognized pathogenetic factor in tissue inflammation and autoimmune disence.

authors

Kröncke KD,Kolb-Bachofen V,Berschick B,Burkart V,Kolb H

doi

10.1016/0006-291x(91)91630-u

subject

Has Abstract

pub_date

1991-03-29 00:00:00

pages

752-8

issue

3

eissn

0006-291X

issn

1090-2104

pii

0006-291X(91)91630-U

journal_volume

175

pub_type

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