Platelet Metal Levels in Normal Subjects Determined by Atomic Absorption Spectrophotometry

Baker, Russell T.; McNeil, John J; Lander, Harry

doi:10.1055/s-0038-1646696

Cited by 19 publications

(3 citation statements)

References 6 publications

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“…6), this implies that triafestin may not act under normal conditions. However, once insect blood‐sucking injures blood vessels, localized increase of free Zn 2+ may occur; Zn 2+ is released from the cytoplasm of the injured cells into the plasma, and platelets secrete granules storing high concentrations of Zn 2+ by contact with exposed extracellular matrix [50–52]. Triafestins may counteract the kallikrein–kinin system in such a microenvironmental milieu.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of plasma kallikrein–kinin system inhibitors from salivary glands of the blood‐sucking insect Triatoma infestans

et al. 2007

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The plasma kallikrein (EC 3.4.21.34)-kinin system plays an important role in the initiation and amplification of surface-mediated, acute inflammatory responses following tissue injury [1][2][3][4]. This system is composed of three serine protease zymogens [prekallikrein (PK), factor XII (FXII) (EC 3.4.21.38) and factor XI] and the nonenzymatic procofactor, high molecular weight kininogen (HK). Kallikrein-kinin system activation is initiated by binding of FXII and a PK-HK complex to a biological activating surface, such as an endothelial cell surface, and is then accelerated by the reciprocal activation of FXII and PK on the surface. Zn 2+ is essential for binding of FXII and HK to a biological activating surface, and induces their conformational changes [5][6][7][8][9][10][11]. Activation of the kallikrein-kinin system results in the release of bradykinin, a primary mediator of acute inflammatory responses [3,4,12]. Bradykinin causes vasodilation, increases microvascular permeability, and enhances pain sensitivity, resulting in inflammatory symptoms such as redness, edema and pain around the injured site. Activated FXII (FXIIa) Keywords factor XII; high molecular weight kininogen; kallikrein-kinin system; salivary gland; Triatoma infestans Two plasma kallikrein-kinin system inhibitors in the salivary glands of the kissing bug Triatoma infestans, designated triafestin-1 and triafestin-2, have been identified and characterized. Reconstitution experiments showed that triafestin-1 and triafestin-2 inhibit the activation of the kallikrein-kinin system by inhibiting the reciprocal activation of factor XII and prekallikrein, and subsequent release of bradykinin. Binding analyses showed that triafestin-1 and triafestin-2 specifically interact with factor XII and high molecular weight kininogen in a Zn 2+ -dependent manner, suggesting that they specifically recognize Zn 2+ -induced conformational changes in factor XII and high molecular weight kininogen. Triafestin-1 and triafestin-2 also inhibit factor XII and high molecular weight kininogen binding to negatively charged surfaces. Furthermore, they interact with both the N-terminus of factor XII and domain D5 of high molecular weight kininogen, which are the binding domains for biological activating surfaces. These results suggest that triafestin-1 and triafestin-2 inhibit activation of the kallikrein-kinin system by interfering with the association of factor XII and high molecular weight kininogen with biological activating surfaces, resulting in the inhibition of bradykinin release in an animal host during insect blood-feeding.Abbreviations APTT, activated partial thromboplastin time; DS 500, dextran sulfate of M r 500

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Section: Discussionmentioning

confidence: 99%

Identification and characterization of plasma kallikrein–kinin system inhibitors from salivary glands of the blood‐sucking insect Triatoma infestans

et al. 2007

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“…It is known that several blood cells (platelets, neutrophils, lymphocytes) have high concentrations of internalized Zn 2+ . The total concentration of Zn 2+ in platelets is 700 μM (48). It may be speculated that activation of the kallikrein/kinin system in vivo is regulated by the ambient Zn 2+ concentration.…”

Section: Initiation Of Activation Of the Plasma Kallikrein/kinin Systmentioning

confidence: 99%

Activation of the Plasma Kallikrein / Kinin System on Endothelial Cells

Røjkjær

1999

Proc Assoc American Phys

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For more than two decades, it has been known that activation of the plasma kallikrein/kinin system only occurs when it is exposed to artificial, negatively charged surfaces. The existence of physiological, negatively charged surfaces has, however, never been demonstrated in vivo. In this report, we describe current knowledge about how the proteins of the plasma kallikrein/kinin system interact with and become activated on cell membranes. In this model, activation of the plasma kallikrein/kinin system on endothelial cells is not initiated by factor XII autoactivation, as seen on artificial surfaces. On endothelial cells, plasma prekallikrein is activated by a membrane-associated cysteine protease. This activation is dependent on the presence of high molecular weight kininogen and an optimal zinc (Zn2+) concentration. Although the initiation of activation of plasma prekallikrein is independent of factor XII, kallikrein-mediated factor XIIa generation, in turn, accelerates the activation of the system. Further kallikrein formed on endothelial cell membranes is capable of cleaving its receptor and native substrate, high molecular weight kininogen, liberating bradykinin and terminating activation. In addition, the kallikrein formed on the surface of endothelial cells results in kinetically favorable activation of prourokinase and, subsequently, plasminogen. Activation of the plasma kallikrein/kinin system on endothelial cells proceeds by a physiological mechanism to initiate cellular fibrinolysis independent of plasmin, fibrin, and tissue-type plasminogen activator.

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“…In addition, fibrinogen receptors can be exposed by proteolytic enzymes such as trypsin, chymotrypsin, and elastase, the tumor promoter, phorbol myristate acetate (PMA), calcium ionophores (reviewed in 14), and zinc (22,23). Zinc is present in platelets at high concentrations (24,25), and has been shown to aggregate washed platelets at concentrations ranging from 0.1 to 0.6mM (22).…”

Section: Introductionmentioning

confidence: 99%

Effect of Stimulation on the Stabilization of Platelet-Fibrinogen Interactions

Peerschke

1992

Thromb Haemost

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SummaryThe interaction between fibrinogen and stimulated platelets is a multiphasic process that culminates in the stabilization of ligand binding and reduced accessibility of bound fibrinogen to exogenous antibody. The present study was designed to further explore platelet-fibrinogen interactions by examining the effect of agonist on bound fibrinogen expression and interaction with stimulated platelets as a function of time after ligand binding. Two agents were identified, Zn2+ and phorbol myristate acetate (PMA), which support progressive decreases in bound fibrinogen expression on platelets, but fail to support the stabilization of fibrinogen binding. Sixty min after binding to platelets, approximately 80% of bound fibrinogen remained reversibly associated with Zn2+- or PMA-treated platelets and failed to associate with the Triton X-100 insoluble cytoskeleton. In contrast, polyclonal anti-fibrinogen antibody binding decreased by more than 66%. Over the same time course, fibrinogen binding to control platelets, stimulated with thrombin or ADP, was not only accompanied by a 70% decrease in antifibrinogen antibody binding, but also an inability of EDTA or excess exogenous fibrinogen to dissociate more than half of platelet-associated fibrinogen, as well as the progressive association of bound fibrinogen with the platelet cytoskeleton. Costimulation of platelets with ZnCl2 and thrombin or ZnCl2 and ADP enhanced overall fibrinogen binding but not the EDTA-resistant component, and prevented the recovery of irreversibly bound fibrinogen with the Triton X-100 insoluble cytoskeleton. Costimulation of PMA- or Zn2+-treated platelets with low doses of A23187, however, restored the stabilization of platelet-fibrinogen interactions. These data suggest that modulation of bound fibrinogen expression on stimulated platelets can occur independently of the development of EDTA-resistant fibrinogen binding, and that stabilization of platelet-fibrinogen interactions is sensitive to stimulation-specific intracellular signal transduction.

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Platelet Metal Levels in Normal Subjects Determined by Atomic Absorption Spectrophotometry

Cited by 19 publications

References 6 publications

Identification and characterization of plasma kallikrein–kinin system inhibitors from salivary glands of the blood‐sucking insect Triatoma infestans

Identification and characterization of plasma kallikrein–kinin system inhibitors from salivary glands of the blood‐sucking insect Triatoma infestans

Activation of the Plasma Kallikrein / Kinin System on Endothelial Cells

Effect of Stimulation on the Stabilization of Platelet-Fibrinogen Interactions

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