Interaction of human plasma kallikrein and its light chain with C.hivin.1 inhibitor

Graaf, F. van der; Koedam, J. A.; Griffin, John H.; Bouma, Bonno N.

doi:10.1021/bi00289a037

Cited by 55 publications

(38 citation statements)

References 42 publications

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“…Second, about one-third of native Cl-Inh in plasma is cleaved in vitro to iCl-Inh upon activation of the contact system by kaolin (53) and DXS (45). Third, analytic gel (SDS-PAGE) studies concerning the interaction of Cl-Inh with either kallikrein, Factor XIa, or plasmin have demonstrated the formation of stable high-molecular weight complexes and the appearance of iCl-Inh species (22,(27)(28)(29)56).…”

Section: Ci-cl-inh and Kallikrein-cl-inh Complexes In Patients Withmentioning

confidence: 99%

“…Several studies have shown that the formation of high-molecular weight target proteinase-C1-Inh complexes is accompanied by the generation of modified (cleaved), inactive Cl-Inh (iCl-Inh) species with a lower apparent molecular weight than native Cl-Inh (23,24,(27)(28)(29). In addition, a number ofendogenous (e.g., neutrophil elastase) and bacterial nontarget proteinases (i.e., proteinases that are not inhibited by Cl-Inh) generate iCl-Inh species by catalytical cleavage ofthe inhibitor in its reactive center (30,31).…”

Section: Introductionmentioning

confidence: 99%

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Proteolytic inactivation of plasma C1- inhibitor in sepsis.

Nuijens¹,

Eerenberg-Belmer²,

Huijbregts³

et al. 1989

J. Clin. Invest.

138

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Activation of both the complement system and the contact system of intrinsic coagulation is implicated in the pathophysiology of sepsis. Because C1 inhibitor (Cl-Inh) (M, 110,000). Elevated iCl-Inh levels (_ 0.13 ,uM) were found in 81% of all patients, sometimes up to 1.6 MM. Levels of iCl-Inh on admission appeared to be of prognostic value: iCl-Inh was higher in 27 patients who died than in 21 patients who survived (P = 0.003). The mortality in 15 patients with iCl-Inh levels up to 0.2,uM was 27%, but in 12 patients with plasma iCl-Inh exceeding 0.44 gM, the mortality was 83%. The overall mortality in the patients with sepsis was 56%. We propose that the cleavage of Ci-Inh in patients with sepsis reflects processes that play a major role in the development of fatal complications during sepsis.

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Section: Ci-cl-inh and Kallikrein-cl-inh Complexes In Patients Withmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proteolytic inactivation of plasma C1- inhibitor in sepsis.

Nuijens¹,

Eerenberg-Belmer²,

Huijbregts³

et al. 1989

J. Clin. Invest.

138

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“…Chemicals used in the purification of factor XI1 and kallikrein were obtained from sources described previously [16,171. Ovalbumin, diisopropylphosphofluoridate and soybean trypsin inhibitor (SBTI) were from Sigma Chemicals (St Louis, MO).…”

Section: Ma Trr Iulsmentioning

confidence: 99%

“…Factor XI1 preparations were homogeneous and pure as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Human plasma kallikrein and its heavy and light chain were purified as described previously [16]. Two-chain high-M, kininogen was purified according the procedure of Kerbiriou and Griffin [18].…”

Section: Proteinsmentioning

confidence: 99%

“…We developed a method do determine kallikrein-dependent factor XI1 activation under conditions where autoactivation contributes to factor XIIa formation. To obtain more insight into the surface-dependent mechanism, we compared the kinetics of factor XI1 activation by kallikrein with that of its isolated light chain, the fragment of kallikrein which contains the active site [16]. We were able to correlate the effect of sulfatides on the rate constants of factor XI1 activation by kallikrein and its light chain with the binding properties of the various reactants to the sulfatide surface.…”

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confidence: 99%

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Surface-dependent activation of human factor XII (Hageman factor) by Kallikrein and its light chain

1985

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In this paper we report the effect of sulfatides on the rate constants of factor XI1 activation by kallikrein and its isolated light chain (the domain of kallikrein that contains the active site of the enzyme). In the absence of sulfatides, kallikrein and the light chain were equally effective in factor XI1 activation (k, = 1.57 x lo3 M ~ ' '-at pH 7.0). The pH optima were the same (pH 7.0) and the reaction was not affected by variation of the ionic strength. Sulfatides strongly increased the rate constants of factor XIIa formation. In the presence of sulfatides kallikrein was, however, much more active than its light chain. At 330 pM sulfatides, p H 7.0 and 100 mM NaCl the rate constants of factor XI1 activation were 5.34 x 10' M -' s-' and 4.17 x lo4 M -' s-' for kallikrein and its light chain, respectively. The pH optimum of factor XI1 activation by kallikrein in the presence of sulfatides was shifted to pH 6.3, and the reaction became highly ionic-strength-dependent. The rate constant increased considerably at decreasing NaCl concentrations. The optimum pH for light-chain-dependent factor XI1 activation in the presence of sulfatides remained unaltered and the reaction was not affected by the ionic strength. Binding studies revealed that both kallikrein and factor XI1 bind to the sulfatide surface, whereas no binding of the light chain of kallikrein was detectable. The isolated heavy chain of kallikrein had the same binding properties as kallikrein, which indicates that the heavy-chain domain contains the functional information for kallikrein binding to sulfatides. Since the effects of pH and ionic strength on the rate constants of kallikrein-dependent factor XI1 activation in the presence of sulfatides correlated with effects on the binding of kallikrein, it is concluded that under these conditions surface-bound factor XI1 is activated by surface-bound kallikrein. Our data suggest that sulfatides stimulate kallikrein-dependent factor XI1 activation by two distinct mechanisms: (a) by making factor XI1 more susceptible to peptide bond cleavage by kallikrein and (b) by promoting the formation of the enzymesubstrate complex through surface binding of kallikrein and factor XII.When human plasma is brought into contact with negatively charged surfaces such as glass, kaolin or sulfatides, contact activation occurs which results in the initiation of intrinsic coagulation, fibrinolysis and kinin formation (for recent reviews see [l, 21). For optimal contact activation the presence of a negatively charged surface and the protein cofactor high-molecular mass kininogen (high-M, kininogen) are essential. Factor XI1 (Hageman factor) is the zymogen of a serine protease that plays a central role in the molecular events occurring during the initial stages of contact activation. Two reactions can contribute to the activation of Factor XI1 in the presence of a negativcly charged surface. Factor XI1 is thought to be involved in a so-called reciprocal activation mechanism in which Factor XIIa activates prekallikrein into kallikr...

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Studies on components of the contact phase system in patients with advanced gastrointestinal cancer

Roeise

Sivertsen

Ruud

et al. 1990

Cancer

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The authors have studied components of the contact system in plasma obtained from patients with advanced gastrointestinal cancer. Plasma samples from 118 healthy blood donors served as controls. Plasma prekallikrein (PKK) values, evaluated by chromogenic peptide substrate technique, were significantly decreased in patients with cancer compared with healthy blood donors. High molecular weight kininogen (HMwK) and Hageman factor (FXII) values, assayed by immunochemical techniques, were also decreased in the patients with cancer. The changes of contact factors were most pronounced in patients with liver metastasis. The most striking observation in our study, however, was the elevated inhibitor values in patients with cancer. Alpha-2-macroglobulin (a2M) and C1 inhibitor (C1INH) values, determined both by functional and immunochemical techniques, were markedly increased in patients with cancer. In conclusion, this study shows that patients with intestinal cancer have reduced values of contact factors and markedly elevated inhibitor values which indicate that development of malignant tumors in the gastrointestinal tract is associated with changes in the contact system of plasma. Cancer 65:1355-1359,1990.

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Interaction of human plasma kallikrein and its light chain with C.hivin.1 inhibitor

Cited by 55 publications

References 42 publications

Proteolytic inactivation of plasma C1- inhibitor in sepsis.

Proteolytic inactivation of plasma C1- inhibitor in sepsis.

Surface-dependent activation of human factor XII (Hageman factor) by Kallikrein and its light chain

Studies on components of the contact phase system in patients with advanced gastrointestinal cancer

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