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Kininogen deficiency modulates chronic intestinal inflammation in genetically susceptible rats.

Abstract
Genetically susceptible Lewis rats injected in the intestinal wall with peptidoglycan-polysaccharide (PG-APS) polymers develop chronic granulomatous enterocolitis concomitant with activation of the kallikrein-kinin system. To elucidate the role of high-molecular-weight kininogen (HK) in chronic enterocolitis, we back crossed Brown-Norway rats having a HK deficiency with Lewis rats for five generations. Two new strains were produced, wild-type F5 (F5WT) and HK deficient (F5HKd), each with a approximately 97% Lewis genome. The HK values of F5WT and F5HKd rat plasma were 0.62 +/- 0.20 and 0.08 +/- 0.03 U/ml, respectively. In PG-APS-injected rats, chronic inflammation was measured by using gross gut score, histological inflammation, liver granuloma, and white blood cell count. The mean gross gut scores were significantly lower in the F5HKd than in the F5WT rats. Plasma T-kininogen was significantly less in F5HKd. These results indicate the importance of the kallikrein-kinin system in this model of chronic enterocolitis and systemic inflammation.
AuthorsIrma Isordia-Salas, Robin A Pixley, Fengling Li, Irma Sainz, R Balfour Sartor, Albert Adam, Robert W Colman
JournalAmerican journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 283 Issue 1 Pg. G180-6 (Jul 2002) ISSN: 0193-1857 [Print] United States
PMID12065305 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Blood Proteins
  • Kininogen, High-Molecular-Weight
  • Peptidoglycan
  • Polymers
  • Polysaccharides
Topics
  • Animals
  • Blood Proteins (analysis)
  • Chronic Disease
  • Enterocolitis (chemically induced, complications, genetics, pathology)
  • Genetic Predisposition to Disease
  • Kallikrein-Kinin System
  • Kininogen, High-Molecular-Weight (deficiency)
  • Metabolism, Inborn Errors (complications)
  • Peptidoglycan
  • Polymers
  • Polysaccharides
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew

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