Chronic intestinal inflammation and angiogenesis in genetically susceptible rats is modulated by kininogen deficiency.
Genetically susceptible Lewis rats injected in the intestinal wall with peptidoglycan-polysaccharide (PG-APS) polymers develop chronic granulomatous enterocolitis associated with activation of the kallikrein-kinin system. To elucidate the role of high-molecular-weight kininogen (HK), we backcrossed Brown Norway rats having an 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 rat plasma and F5HKd rat plasma were 0.62 +/- 0.20 and 0.08 +/- 0.03 U/ml, respectively. Among the inflammatory changes, the mean gross gut, total intestinal histologic and liver granuloma score and the white blood count were significantly lower in the F5HKd than the F5WT rats. Plasma T-kininogen was significantly less in F5HKd. Angiogenesis (mean vascular density) in the cecum was decreased significantly in F5HKd compared to F5WT. 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, 3400 North Broad Street, Philadelphia, PA 19140, USA.
Pixley
Robin A
RA
Li
Fengling
F
Sainz
Irma
I
Balfour Sartor
R
R
Adam
Albert
A
Colman
Robert W
RW
D000818:Animals; D001483:Base Sequence; D002432:Cecum / Q000098:blood supply; D004760:Enterocolitis / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000503:physiopathology; D016234:Kallikrein-Kinin System / Q000235:genetics / Q000502:physiology; D019679:Kininogen, High-Molecular-Weight / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew
D019679:Kininogen, High-Molecular-Weight