Selective kallikrein-kinin system activation in inbred rats differentially susceptible to granulomatous enterocolitis

Abstract

Selective in vivo and in vitro activation of the contact system in susceptible Lewis rats suggests that this pathway is one determinant of genetic susceptibility to granulomatous enterocolitis and systemic complications.

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

“…account for at least half of the diversity of bacteria in the colon (64,65). In genetically susceptible rats, intramural injection of PGN results in granulomatous inflammatory bowel disease (66,67). Animal models of inflammatory bowel disease such as the IL-10 knockout mouse reconstituted with Gram-positive Enterococcus faecalis develop chronic intestinal inflammation (68,69).…”

Suppression of Dextran Sulfate Sodium-Induced Colitis in Kininogen-Deficient Rats and Non-peptide B2 Receptor Antagonist-Treated Rats

“…Furthermore, the involvement of the kallikrein-kinin system in the development of experimental IBD models that mimic human Crohn's disease was also reported (8,9,35). Although it was reported that the activation of the plasma kallikrein-kinin system was evaluated from the consumption of plasma prekallikrein and high-molecularweight kininogen (8,35), the actual contribution of kinins to enterocolitis should be tested using adequate biological and pharmacological approaches (36).…”

“…To our knowledge, in spite of the potent proinflammatory activity of kinins, the involvement of the kallikrein-kinin system in the development of experimental enterocolitis (8,9,22) and colitis (4) has been demonstrated, but the number of reports is limited. In a model of granulomatous enterocolitis induced in a genetically susceptive strain of Lewis rats by peptidoglycan-polysaccharide polymers isolated from group A streptococci, the activation of the plasma kallikrein kinin system was presumed to have occurred, because of the consumption of the precursor proteins plasma prekallikrein and high-molecular-weight kininogen (9, 23 -25).…”

The mutation Ser511Asn leads to N-glycosylation and increases the cleavage of high molecular weight kininogen in rats genetically susceptible to inflammation

“…8 The Lewis rat is clearly more susceptible to develop chronic intestinal and systemic inflammation than the Buffalo and the Fischer 344 rat. 9 However, the genes involved in these differences have not yet been identified. We developed a rat model of chronic granulomatous enterocolitis by injecting purified bacterial cell wall polymers, peptidoglycan polysaccharide from group A streptococci (PG-APS), into the intestinal wall.…”

“…Female Lewis rats, the highest responders, develop biphasic intestinal inflammation with an acute phase that peaks 2 to 4 days after PG-APS injection and gradually decreases over the next 10 days. 9,13 The enterocolitis spontaneously reactivates on days 12 to 14 accompanied by T-lymphocytemediated peripheral erosive arthritis, granulomatous hepatitis, normochromic anemia, and leukocytosis.…”