BACKGROUND: The objective of this study was to characterize the acute and chronic inflammation induced by the intramural injection of peptidoglycan-polysaccharide (PG-PS) into the distal colon of genetically susceptible rats. METHODS: Blood-to-lumen clearance of 51Cr-ethylenediaminetetraacetic acid, colonic myeloperoxidase activity, colon weight, and plasma nitrite and nitrate levels were determined to quantitate colonic mucosal injury, inflammation, and nitric oxide (NO) production, respectively. RESULTS: Intramural injection of PG-PS into the distal colon produced a local biphasic inflammatory response composed of an acute episode 3 days after injection; this was followed by a spontaneous reactivation of chronic granulomatous colitis manifested by colonic thickening, adhesions, and infiltration of the submucosa and muscularis propria with macrophages, neutrophils, and lymphocytes at 3-4 weeks. Mucosal ulcers were evident only at 3 weeks, but hepatic nodules, splenic necrosis, and arthritis were evident at both 3 and 4 weeks after PG-PS injection. PG-PS produced significant increases in colonic mucosal permeability, myeloperoxidase activity, and plasma nitrite and nitrate levels at 3 weeks postinjection compared with controls. PG-PS stimulated the production of nitrite by elicited peritoneal macrophages and neutrophils in vitro. CONCLUSIONS: PG-PS produces a chronic granulomatous colitis in rats; this colitis is characterized by enhanced NO production.
BACKGROUND: The objective of this study was to characterize the acute and chronic inflammation induced by the intramural injection of peptidoglycan-polysaccharide (PG-PS) into the distal colon of genetically susceptible rats. METHODS: Blood-to-lumen clearance of 51Cr-ethylenediaminetetraacetic acid, colonic myeloperoxidase activity, colon weight, and plasma nitrite and nitrate levels were determined to quantitate colonic mucosal injury, inflammation, and nitric oxide (NO) production, respectively. RESULTS: Intramural injection of PG-PS into the distal colon produced a local biphasic inflammatory response composed of an acute episode 3 days after injection; this was followed by a spontaneous reactivation of chronic granulomatous colitis manifested by colonic thickening, adhesions, and infiltration of the submucosa and muscularis propria with macrophages, neutrophils, and lymphocytes at 3-4 weeks. Mucosal ulcers were evident only at 3 weeks, but hepatic nodules, splenic necrosis, and arthritis were evident at both 3 and 4 weeks after PG-PS injection. PG-PS produced significant increases in colonic mucosal permeability, myeloperoxidase activity, and plasma nitrite and nitrate levels at 3 weeks postinjection compared with controls. PG-PS stimulated the production of nitrite by elicited peritoneal macrophages and neutrophils in vitro. CONCLUSIONS:PG-PS produces a chronic granulomatous colitis in rats; this colitis is characterized by enhanced NO production.
Authors: Karen L Reed; A Brent Fruin; Adam C Gower; Kelly D Gonzales; Arthur F Stucchi; Christopher D Andry; Michael O'Brien; James M Becker Journal: Dig Dis Sci Date: 2005-12 Impact factor: 3.199