Activation of Purified Human Plasma Prekallikrein Triggered by Cell Wall Fractions of Escherichia coli and Staphylococcus aureus

Es, Kalter; Wc, van Dijk; Timmerman, A.; Verhoef, J.; Bn, Bouma

doi:10.1093/infdis/148.4.682

Cited by 77 publications

(38 citation statements)

References 40 publications

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“…29 contact pathway participates in host responses to pathogens. Consistent with this concept, several microbial activators of the contact pathway have been identified, including bacterial surface proteins, 68,69 lipopolysaccharide, 70 teichoic/lipoteichoic acid, 70 and, as discussed here, long-chain polyP. 5,27 The first reported role for polyP in blood clotting was a 2006 study from our laboratory that showed that polyP is strongly procoagulant, triggering clotting of plasma via the contact pathway as well as modulating downstream clotting reactions (see, in particular, step 1 in Figure 2A).…”

Section: Polyp In Plateletsmentioning

confidence: 71%

Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation

Morrissey

Choi

Smith

2012

Blood

338

295

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AbstractInorganic polyphosphate is widespread in biology and exhibits striking prohemostatic, prothrombotic, and proinflammatory effects in vivo. Long-chain polyphosphate (of the size present in infectious microorganisms) is a potent, natural pathophysiologic activator of the contact pathway of blood clotting. Medium-chain polyphosphate (of the size secreted from activated human platelets) accelerates factor V activation, completely abrogates the anticoagulant function of tissue factor pathway inhibitor, enhances fibrin clot structure, and greatly accelerates factor XI activation by thrombin. Polyphosphate may have utility as a hemostatic agent, whereas antagonists of polyphosphate may function as novel antithrombotic/anti-inflammatory agents. The detailed molecular mechanisms by which polyphosphate modulates blood clotting reactions remain to be elucidated.

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Section: Polyp In Plateletsmentioning

confidence: 71%

Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation

Morrissey

Choi

Smith

2012

Blood

338

295

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“…Cell wall components of Gram-negative bacteria (e.g., endotoxin) and Gram-positive bacteria (e.g. peptidoglycan) can activate both the complement system and the contact system of intrinsic coagulation (2,3). Considerable evidence has accumulated that excessive activation of these cascade systems, with release of biologically active peptides (anaphylatoxines and bradykinin), plays a role in the pathophysiology of sepsis, notably Receivedfor publication 7 July 1988 and in revisedform 24 February 1989. when complicated by shock and/or adult respiratory distress syndrome (4)(5)(6)(7)(8)(9)(10)(11)(12).…”

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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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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“…However, the aprotinin plasma levels in our experiments exceeded 468 KIU/mL (10 ^mol/L) and should therefore have blocked relevant amounts of plasma kallikrein in the circulation. 2 ' 28 This notion is supported by a previous study in which high amounts of plasma kallikrein, rapidly generated in an in vivo model of dextran sulfate-induced activation of the contact phase of coagulation, were completely blocked at an aprotinin concentration of 400 KIU/mL. 29 Since the extent of kininogen cleavage was not influenced by administration of aprotinin, the question arises why aprotinin then attenuated arterial hypotension.…”

mentioning

confidence: 85%

“…1,2 Arterial hypotension is induced by LPS in many species of experimental animals. Both the contact and the complement systems have been found to be activated in patients with septic shock.…”

mentioning

confidence: 99%

Inhibition of Plasma Kallikrein With Aprotinin in Porcine Endotoxin Shock

Siebeck

Fink²,

Weipert³

et al. 1993

The Journal of Trauma: Injury, Infection, and Critical Care

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Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 /xg/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 pmo\, was given IV during 8 hours, resulting in plasma levels above 10 ^mol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% ± 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% ± 11% vs. 68% ± 8%; mean ± SEM; p = 0.026). Fibrin monomer and C3a<*,Arg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock.BACTERIAL LIPOPOLYSACCHARIDE (LPS) is regarded as one of the causative agents of gram-negative sepsis and has been demonstrated to activate the contact phase of the intrinsic blood coagulation cascade in vitro. 1,2Arterial hypotension is induced by LPS in many species of experimental animals. Both the contact and the complement systems have been found to be activated in patients with septic shock. 3Activation of the contact system of blood coagulation ( Fig. 1) occurs as reciprocal activation of plasma kallikrein and Hageman factor (factor XII) in the presence of a negatively charged surface and high molecular weight kininogen (HMr kininogen) as cofactors. The potent hypotensive oligopeptide bradykinin has been implicated in the pathophysiology of shock.9 Decreased kininogen and prekallikrein concentrations 10 and elevated kinin levels 11 in plasma have been repeatedly described in experimental LPS shock and in patients with septic shock. Using a specific kinin receptor antag- onist it was demonstrated that kinins mediate LPSinduced arterial hypotension in rats. 12According to these results generation of active plasma kallikrein by contact system activation and subsequent release of bradykinin could play an important role in the pathophysiology of LPS-induced shock. To test this hypothesis we investigated whether in vivo inhibition of plasma kallikrein with aprotinin, a plasma kallikrein inhibitor, 13 would block or attenuate the effect of LPS on blood pressure and the concentration of uncleaved kininogen in pigs. Further questions concerned the effect of aprotinin on LPS-induced respiratory failure and on activation of the complement and coagulation systems. MATERIALS AND METHODSMiniature pigs (Medical Service GmbH, Munich) with a body weight ranging from 18.0 to 22....

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Activation of Purified Human Plasma Prekallikrein Triggered by Cell Wall Fractions of Escherichia coli and Staphylococcus aureus

Cited by 77 publications

References 40 publications

Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation

Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation

Proteolytic inactivation of plasma C1- inhibitor in sepsis.

Inhibition of Plasma Kallikrein With Aprotinin in Porcine Endotoxin Shock

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