Mobilization of tissue kallikrein in inflammatory disease of the colon

Abstract

SUMMARY Colonic tissue was taken at operation from 10 patients with active ulcerative colitis and three patients with uncomplicated diverticular disease but with severe symptoms. Levels of kininogen, kallikrein, and kallikrein precursor were measured in blood-free tissue samples. In normal colon tissue a kininogen occurred in the muscle and none was detected in the mucosa. Kallikrein and its precursor were found in mucosa but not in muscle. In acutely inflamed tissue from ulcerative colitis patients relatively high levels of active kallikrein were detected in the underlying colonic muscle. There was little change in the level of kallikrein in inflamed mucosa or of kininogen in the muscle of these patients. No kallikrein was found in colonic muscle from patients with diverticular disease and the mucosal kallikrein level in these patients was unchanged. The findings suggest a mechanism for the formation of kinins in the wall of the colon which is present in ulcerative colitis but not in diverticular disease.

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

“…Zeitlin and Smith reported relatively high levels of active tissue kallikrein in acutely inflamed tissue from UC patients, suggesting that kinins can be generated from lowmolecular-weight kininogen during active human disease (12). 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).…”

“…1), in the presence of DSS, kinin generation occurred in plasma taken from SD and BN-Ki, but not in that from BN-Ka. In contrast, the epithelial cells of the intestine were reported to contain the tissue kallikrein (12,22,43,44). Once the damage to the intestinal mucosa is induced, the tissue kallikrein may be released from the epithelial cells (43).…”

“…Alternatively, the stimuli to increase the secretion of kallikrein during DSS-treatment may also facilitate the release of tissue kallikrein. It cannot be ruled out that the released tissue kallikrein may also generate kinins from low molecular weight kininogen, since the intestine is rich in tissue kallikrein (12,22,43,44).…”

“…Various physiological or pathological conditions such as tissue damage, ischemia, heat, cold, low pH, and negatively charged surfaces can activate i) the plasma kallikrein-kinin system via the Hageman factor to release bradykinin and ii) the tissue kallikrein-kinin system via the release or secretion of tissue kallikrein (10). BK is a very potent mediator of vasodilatation and vascular permeability (10), the most potent chemical mediator of pain sensation (10,11), and a major spasmogen in the smooth muscle of many organs including the gut (10,12,13). These direct actions of BK may at least partly explain the pathogenesis of UC.…”

Kallikrein – Kinin System and Coagulation System in Inflammatory Bowel Diseases

“…Long time ago only one study (Zeitlin & Smith, 1973) reported the presence of tissue kallikrein in normal human colon and a higher concentration in the inflamed colon of patients with UC. In rat model of PG -APS stimulated chronic inflammation we have shown that the normal location of ITK was the goblet cells and substantial amounts of ITK were present in the macrophages of the granulomas found in the submucosa indicating that ITK is present at the site of inflammation .…”