Plasma and tissue kallikrein in arthritis and inflammatory bowel disease.
To ascertain the participation of the plasma kallikrein-kinin system (KKS) in arthritis and inflammatory bowel disease, we used two rat models resembling rheumatoid arthritis and Crohn's disease. Proteoglycan-polysaccharide from group A streptococcus (PG-APS) produced chronic destructive inflammation and systemic response in the genetically susceptible Lewis rat, in the joints when injected intraperitoneally and in the bowel when injected into the gut wall. In both models, the KKS is activated, as evidenced by decreased prekallikrein, factor XI and high molecular weight kininogen. A specific plasma kallikrein inhibitor, Bz-Pro-Phe-boroarginine, reverses the plasma changes as well as the clinical gross and microscopic pathology of both the experimental arthritis and the inflammatory bowel disease in the genetically susceptible rats. We have also shown that the tissue kallikrein system is involved in the intestinal inflammatory changes. Intestinal tissue kalikrein (ITK) is localized in goblet cells in both normal and inflamed tissue. In chronic granulomatous inflammation, ITK is localized in macrophages. ITK decreases in chronic inflammation, probably due to secretion, since the mRNA is unchanged. Kallikrein binding protein, the ITK inhibitor, decreases due to enzyme-inhibitor complexes. Both plasma and tissue kallikrein are appealing targets for drug therapy of rheumatoid arthritis and Crohn's disease.
Colman
R W
RW
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA. colmanr@astro.temple.edu
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology*; D004195:Disease Models, Animal; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000209:etiology*; D007422:Intestines / Q000737:chemistry; D020842:Plasma Kallikrein / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D011135:Polysaccharides, Bacterial / Q000633:toxicity; D011509:Proteoglycans / Q000633:toxicity; D051381:Rats; D011917:Rats, Inbred Lew; D020840:Tissue Kallikreins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*
D011135:Polysaccharides, Bacterial; D011509:Proteoglycans; D020842:Plasma Kallikrein; D020840:Tissue Kallikreins