Mucosal injury and inflammation in a model of chronic granulomatous colitis in rats

Gastroenterology. 1993 Mar;104(3):759-71. doi: 10.1016/0016-5085(93)91011-6.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / biosynthesis
  • Animals
  • Chronic Disease
  • Colitis / chemically induced*
  • Colitis / metabolism
  • Colitis / pathology
  • Crohn Disease / etiology
  • Disease Models, Animal*
  • Enzyme Induction
  • Female
  • Granuloma / chemically induced*
  • Granuloma / metabolism
  • Granuloma / pathology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Nitric Oxide Synthase
  • Peptidoglycan
  • Peroxidase / metabolism
  • Rats
  • Rats, Inbred Lew
  • Streptococcus pyogenes


  • Peptidoglycan
  • Peroxidase
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases