title: 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.
authors.affiliation: The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Irma
authors.initials: I
authors.lastname: Isordia-Salas
authors.forename: Robin A
authors.initials: RA
authors.lastname: Pixley
authors.forename: Fengling
authors.initials: F
authors.lastname: Li
authors.forename: Irma
authors.initials: I
authors.lastname: Sainz
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
authors.forename: Albert
authors.initials: A
authors.lastname: Adam
authors.forename: Robert W
authors.initials: RW
authors.lastname: Colman
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D002908:Chronic Disease; D004760:Enterocolitis / Q000139:chemically induced / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D016234:Kallikrein-Kinin System; D019679:Kininogen, High-Molecular-Weight / Q000172:deficiency*; D008661:Metabolism, Inborn Errors / Q000150:complications*; D010457:Peptidoglycan; D011108:Polymers; D011134:Polysaccharides; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew
chemical_list: D001798:Blood Proteins; D019679:Kininogen, High-Molecular-Weight; D010457:Peptidoglycan; D011108:Polymers; D011134:Polysaccharides