Glycosaminoglycans affect the action of human plasma kallikrein on kininogen hydrolysis and inflammation
Data
2002-12-01
Autores
Carmona, Adriana Karaoglanovic 
Nader, Helena Bonciani
Dietrich, Carl Peter
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Human plasma kallikrein (huPK) is a serine proteinase involved in many biological processes including those of the kallikrein-kinin system. The action of huPK on kininogen results in bradykinin (BK) release, a potent mediator of inflammatory responses. BK generation may be influenced by several agents, and the aim of this work was to investigate the effect of glycosaminoglycans (GAGs) on human high-molecular-weight kininogen (HK) hydrolysis by huPK and on inflammation.huPK was pre-incubated in the absence and presence of different GAGs, followed by the addition of kininogen. Bradykinin released at different times was measured by radioimmunoassay, and K-M and k(cat) were calculated. Tuna and bovine dermatan sulfates, the most potent GAGs studied, reduced by 80% and 68%. respectively, the catalytic efficiency of huPK (control=4.1 x 10(4) M-1 s(-1)) in BK release.The effect of bovine dermatan sulfate (BDS) on inflammatory response was studied in rat paw edema induced by carrageenin and hourly determined (1-4 h) by plethysmography. BDS significantly reduced the inflammatory response in the first and second hours of measurements (24% and 28%, respectively), p < 0.05.GAGs were shown to reduce bradykinin release in vitro and in an inflammation model. This reduction may play a role in the control or maintenance of some pathological and physiological processes. (C) 2002 Published by Elsevier Science B.V.
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International Immunopharmacology. Amsterdam: Elsevier Science Bv, v. 2, n. 13-14, p. 1861-1865, 2002.