S. Aiko et Mb. Grisham, SPONTANEOUS INTESTINAL INFLAMMATION AND NITRIC-OXIDE METABOLISM IN HLA-B27 TRANSGENIC RATS, Gastroenterology, 109(1), 1995, pp. 142-150
Background & Aims: It has been reported that transgenic rats expressin
g the HLA-B27 and the beta(2)-microglobulin genes develop spontaneous
gastrointestinal (GI) inflammation; however, no systematic or quantita
tive evaluation of this GI inflammation has been reported. Therefore,
the objective of this study was to characterize quantitatively the GI
injury and inflammation observed in commercially available HLA-B27 tra
nsgenic vats. Methods: HLA-B27 rats and Fisher 344 male controls were
used for these studies. Gastric, ileal, and colonic blood-to-lumen cle
arances of Cr-51-ethylenediaminetetraacetic acid, tissue myeloperoxida
se activities, and wet/dry ratios of the various tissues as well as pl
asma nitrate and nitrite levels were quantified for each control and t
ransgenic animal. Results: Spontaneous ileitis and colitis developed i
n 5 of 10 HLA-B27 transgenic vats beginning at approximately 17 weeks
of age and persisting for an additional 13 weeks. Increases in mucosal
permeability and myeloperoxidase activities as well as histological a
nalysis showed intestinal injury and chronic inflammation. Plasma leve
ls of nitrate and nitrite, the stable decomposition products of nitric
oxide, were found to be significantly enhanced (fourfold) only in tho
se rats that developed the intestinal inflammation. Conclusions: The c
hronic ileitis and colitis observed in HLA-B27 transgenic rats seems t
o be associated with enhanced NO metabolism.