Kininogen deficiency modulates chronic intestinal inflammation in genetically susceptible rats.
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.
Isordia-Salas
Irma
I
The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Pixley
Robin A
RA
Li
Fengling
F
Sainz
Irma
I
Sartor
R Balfour
RB
Adam
Albert
A
Colman
Robert W
RW
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
D001798:Blood Proteins; D019679:Kininogen, High-Molecular-Weight; D010457:Peptidoglycan; D011108:Polymers; D011134:Polysaccharides