Plasma kallikrein

Dennis, M.S., Herzka, A., Lazarus, R.A. Potent and selective Kunitz domain inhibitors of plasma kallikrein designed by phage display. /. Biol. Chem. 270 25411-25417, 1995. 

H-kininogen Plasma kallikrein bradykinin (RPPGFSPFR) B2 receptor... 

In rare cases of a systemic release, kinins have the potential to cause severe hypotension. Uncontrolled activation of the contact system (Fig. 3) is thought to trigger a massive formation of kinins under certain pathological conditions [3]. For instance, this situation is seen in patients with underlying diseases such as systemic inflammatory response syndrome (SIRS) due to sepsis or trauma. SIRS progression is accompanied by depletion of contact system factors and low levels of H-kininogen and plasma kallikrein are indicative of a... 

Factor Xlla converts prekallikrein to kallikrein and kallikrein cleaves HK to generate bradykinin. There is also an important positive feedback in the system in which the kallikrein generated rapidly converts unactivated factor XII to activated factor XII, and the rate of this reaction is hundreds of times faster than the rate of autoactivation [11]. Therefore, much of the unactivated factor XII can be cleaved and activated by kallikrein. Cl inhibitor inhibits all functions of factor Xlla and it is one of two major plasma kallikrein inhibitors. Thus all functions of kallikrein are also inhibited, including the feedback activation of factor XII, the cleavage of HK, and the activation of plasma pro-urokinase [66] to lead to plasmin formation. Cl inhibitor also inhibits the fibrinolytic enzyme plasmin, although it is a relatively minor inhibitor compared to a2-antiplasmin or a2-macroglobulin. 

Mori K, Nagasawa S Studies on human high molecular weight (HMW) kininogen. If. Structural change SS of HMW kininogen by the action of human plasma kallikrein. J Biochem 1981 89 1465-1473. 

Cochrane CG. Revak SD Dissemination of contact activation in plasma by plasma kallikrein. J Exp Med 1980 152 608-619. 

Ichinose A, Fujikawa K, Suyama T The activation 80 of pro-urokinase by plasma kallikrein and its inactivation by thrombin. J Biol Chem 1986 261 3486-3489. 81... 

Bacterial products such as lipopolysaccharides (endotoxins) and cytokines (IL-2) are able to activate the contact system in vitro and in vivo (D9, H4, H7, M41). Immediately after severe trauma or after surgical intervention and particularly during sepsis, a reduction of plasma contact system proteins has been found (C10, K1, N9). Gel filtration studies of plasma demonstrated that plasma PK after activation becomes complexed with a2-M and Cl-Inh (W4). These complexes are rapidly eliminated from the circulation in vivo. In experimental studies in which pulmonary insufficiency was induced in dogs, a significant reduction of plasma kallikrein inhibitors was observed together with reduced HMK. Analysis of the relation be-... 

Human plasma kallikrein has also been described as being directly chemotactic for human neutrophils (57). Kallikrein incubated with the complement component C5 generates chemotactic activity, providing a further mechanism for C5 activation. C5a is the most active and probably the most biologically important of the complement derived chemotactic and anaphylatoxic peptides. 

Plasma kallikrein [EC 3.4.21.34], also known as kinino-genin and serum kallikrein, catalyzes the hydrolysis of Arg—Xaa and Lys—Xaa bonds in polypeptides. This includes the Lys—Arg and Arg—Ser bonds in human kininogen, thus producing bradykinin. Tissue kallikrein [EC 3.4.21.35] catalyzes the hydrolysis of peptide bonds, preferentially Arg—Xaa, in smaU-molecule substrates. It catalyzes the breaking of the appropriate bonds in kininogen resulting in the release of lysyl-bradykinin. 

Tincture of the dried seed, on agar plate at a concentration of 30 p,L/disc, was inactive on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Extract of 10 g plant material in 100 mL ethanol was used b Anticoagulation activity. Serpin BSZx (an inhibitor of trypsin and chemotrypsin) inhibited thrombin, plasma kallikrein, factor Vlla/tissue factor, and factor Xa at heparin-independent association rates. Only factor Xa turned a significant fraction of BSZx over as substrate. Activated protein C and leukocyte elastase were slowly inhibited by BSZx, whereas factor Xlla, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein, and elastase were not or only weakly affected. Trypsin from Fusarium was not inhibited, while interaction with subtilisin Carlsberg and Novo was rapid, but most BSZx was cleaved as a substrate L... 

This pentasaccharide sequence induces a conformational change in AT III which probably causes the complex to be more accessible to the active site of the proteases. The most relevant protease affected by the pentasaccharide 3 is factor Xa, but factor Xlla and plasma kallikrein activities can also be potentiated. Sequence 3 occurs in heparin as well as in various heparan sulfate proteoglycans of different origin including the vascular endothelium. 

Kallikreins are present in plasma and in several tissues, including the kidneys, pancreas, intestine, sweat glands, and salivary glands. Plasma prekallikrein can be activated to kallikrein by trypsin, Hageman factor, and possibly kallikrein itself. In general, the biochemical properties of tissue kallikreins are different from those of plasma kallikreins. Kallikreins can convert prorenin to active renin, but the physiologic significance of this action has not been established. 

Each kinin is formed from a kininogen by the action of a different enzyme. Bradykinin is released by plasma kallikrein, lysylbradykinin by tissue kallikrein, and methionyllysylbradykinin by pepsin and pepsin-like enzymes. The three kinins have been found in plasma and urine. Bradykinin is the predominant kinin in plasma, whereas lysylbradykinin is the major urinary form. 

Another kinin, Lys-bradykinin (also known as kallidin), is produced via the action of the tissue-kallikrein enzyme on LMWK. This enzyme is found in many tissues, either in the form of a precursor requiring activation or as an active enzyme. In contrast to plasma kallikrein, which preferentially acts upon HMWK, tissue kallikrein can release kallidin from either HMWK or LMWK. Through the action of aminopeptidases, kallidin can subsequently be converted directly into bradykinin. This enzyme is present in both the plasma and on the surface of epithelial cells. 

Its mechanism of action, however, is not completely elucidated. Kamakura et aL [94] studied the effects of stem bromelain on tlw plasma kallikrein system, bradykinin levels and plasma exudation at the inflammatory site in rats with a kaolin-induced inflammation of an air couch. Bromelain caused a dose-... 

The anti-inflaminatory action of bromelain preparations is the result of dif-fjrjnt mechanisms thatnft simultaneous 11. First there is, as described sbevr, the depletion of the plasma kallikrein system, inhibiting the generation of bndykinin, a known chemical mediator of inflammation. Second, there is a negative action... 

Human type I interleukin I receptor Human plasma kallikrein and human trombin... 

Markland W, Ley AC, Ladner RC. Iterative optimization of high-affinity protease inhibitors using phage display, 2. Plasma kallikrein and thrombin, Biochemistry, 35 8058-8067, 1996. 

Morishita H, Yamakawa T, Matsusue T, Kusuyama T, Sameshima-Aruga R, Hirose J, et al. Novel factor Xa and plasma kallikrein inhibitory activities of the second Kunitz-type inhibitory domain of urinary trypsin inhibitor. Thromb Res 1994 73 193-204. 

A. R, Joseph, K and Silverberg, M., Pathways for bradykinin formation and inflammatory diseases, J. Allergy Clin. Immunol. 109,195-209,2002 Shariat-Madar, Z., Mahdi, F, and Schmaier, A.H., Assembly and activation of the plasma kallikrein/kinin system a new interpretation, Int. Immunop-harmacol. 2, 1841-1849, 2002 Langbein, L. and Schweizer, J., Keratins of the human hair follicle, Int. Rev. Cytol. 243, 1-78, 2005 Gusterson,... 

Incubation of C3 and C4 for 60 minutes at 37°C with a number of enzymes involved in coagulation and fibrinolysis indicated that half of the enzymes tested were able to cleave C3 and C4 (Table II). Interestingly, factors IXa and Xlla (P-Xlla) did not seem to cleave C3 or C4, whereas factors XIa and Xa, thrombin, plasma kallikrein and plasmin clearly degraded both complement factors. 

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