Glycosaminoglycans affect the action of human plasma kallikrein on kininogen hydrolysis and inflammation.
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 KM and kcat 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. 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.
Gozzo
Andrezza J
AJ
Department of Biochemistry, UNIFESP, EPM, São Paulo, SP, Brazil.
Nunes
Viviane A
VA
Carmona
Adriana K
AK
Nader
Helena B
HB
von Dietrich
Carl Peter
CP
Silveira
Vera L F
VL
Shimamoto
Kazuaki
K
Ura
Nobuyuki
N
Sampaio
Misako U
MU
Sampaio
Claudio A M
CA
Araújo
Mariana S
MS
D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D002351:Carrageenan; D003871:Dermatan Sulfate / Q000494:pharmacology / Q000627:therapeutic use*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007700:Kinetics; D019679:Kininogen, High-Molecular-Weight / Q000737:chemistry / Q000378:metabolism; D008297:Male; D020842:Plasma Kallikrein / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018836:Inflammation Mediators; D019679:Kininogen, High-Molecular-Weight; D003871:Dermatan Sulfate; D002351:Carrageenan; D020842:Plasma Kallikrein; D001920:Bradykinin