Surface-mediated defense reactions. The plasma contact activation system.

Colman, Robert W.

doi:10.1172/jci111326

Cited by 234 publications

(100 citation statements)

References 51 publications

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“…However, a large body of evidence supports the important role of HK and thus the contact system in body defenses (Colman, 1984). Synthetic peptides blocking or disrupting the interaction of HK with anionic surfaces may be useful to elucidate its primary or secondary role and as potential therapeutic agents in pathologic conditions in which activation of the contact system is known to occur.…”

Section: Discussionmentioning

confidence: 99%

The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc‐dependent binding to an anionic surface

Dela

Colman

1992

Protein Science

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The histidine-glycine-rich region of the light chain of cleaved high molecular weight kininogen (HK) is thought to be responsible for binding to negatively charged surfaces and initiation of the intrinsic coagulation, fibrinolytic, and kinin-forming systems. However, the specifically required amino acid sequences have not been delineated. An IgG fraction of a monoclonal antibody (MAb) CllCl to the HK light chain was shown to inhibit by 66% the coagulant activity and by 57% the binding of HK to the anionic surface of kaolin at a concentration of 1.5 pM and 27 pM, respectively. Proteolytic fragments of HK were produced by successive digestion with human plasma kallikrein and factor XIa (FXIa). Those polypeptides that bound tightly (Kd = 0.77 nM) to a C11C1 affinity column were eluted at pH 3.0 and purified by membrane filtration. On 15% SDS polyacrylamide electrophoresis, the approximate M, was 7.3 kDa (range 6.2-8.1 kDa). Based on N-terminal sequencing, this polypeptide (I2), which extends from the histidine residue 459 to a lysine at position 505, 509, 51 1, 512, 515, or 520, inhibits by 50% the coagulant activity expressed by HK at a concentration of 22 pM. The synthetic peptide HGLGHGH representing the N-terminal of the l2 fragment was synthesized, tested, and found at 4 mM to inhibit the procoagulant activity of HK 50%. A synthetic heptadecapeptide, HGLGHGHEQQHGLGHGH (residues 459-475) included within the l2 fragment, and with the ability to bind zinc, inhibited 50% of the HK coagulant activity at a concentration of 325 pM in the absence and presence of added Zn2+ (30 pM). The specific binding of 12'I-HK to a negatively charged surface (kaolin) was inhibited 50% by unlabeled HK (5 pM). HGLGHGH, at a concentration of 7.0 mM, inhibited the binding to kaolin by 50%. The heptadecapeptide inhibited the specific binding of I2'I-HK to kaolin by 50%, at a concentration of 2.3 mM, in the absence of Zn2+.In contrast, when Zn2+ was added, the concentration to achieve 50% inhibition decreased to 630 pM, indicating that Zn2+ was required to attain a favorable conformation for binding. Moreover, the I, fragment was found to inhibit 50% of the I2'I-HK binding to kaolin at a concentration of 380 pM. These results suggest that residues contained within the 1, fragment, notably HGLGHGHEQQHGLGHGH, serves as a primary structural feature for binding to a negatively charged surface.

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Section: Discussionmentioning

confidence: 99%

The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc‐dependent binding to an anionic surface

Dela

Colman

1992

Protein Science

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“…One potential application is the blockage of the plasmin-dependent invasion of cancer cells into surrounding tissue (20). In addition, placental bikunin may be useful for the reduction of severity of brain edema secondary to brain or spinal chord injury (21,22), a process that may result from the local release of the vasodilator bradykinin (21)(22)(23) through the actions of serine proteases such as kallikrein (24).…”

Section: -43mentioning

confidence: 99%

Characterization of Placental Bikunin, a Novel Human Serine Protease Inhibitor

Delaria¹,

Muller²,

Marlor³

et al. 1997

Journal of Biological Chemistry

102

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We reported previously the cloning of a novel human serine protease inhibitor containing two Kunitz-like domains, designated as placental bikunin, and the subsequent purification of a natural counterpart from human placental tissue (Marlor, C. W., Delaria, K. A., Davis, G., Muller, D. K., Greve, J. M., and Tamburini, P. P. (1997) J. Biol. Chem. 272, 12202-12208). In this report, the 170 residue extracellular domain of placental bikunin (placental bikunin (1-170) ) was expressed in baculovirus-infected Sf9 cells using its putative signal peptide. The resulting 21.3-kDa protein accumulated in the medium with the signal peptide removed and could be highly purified by sequential kallikrein-Sepharose and C 18 reverse-phase chromatography. To provide insights as to the potential in vivo functions of this protein, we performed an extensive investigation of the inhibitory properties of recombinant placental bikunin (1-170) and both of its synthetically prepared Kunitz domains. All three proteins inhibited a number of serine proteases involved in the intrinsic pathway of blood coagulation and fibrinolysis. Placental bikunin (1-170) formed inhibitor-protease complexes with a 1:2 stoichiometry and strongly inhibited human plasmin (K i ‫؍‬ 0.1 nM), human tissue kallikrein (K i ‫؍‬ 0.1 nM), human plasma kallikrein (K i ‫؍‬ 0.3 nM) and human factor XIa (K i ‫؍‬ 6 nM). Conversely, this protein was a weaker inhibitor of factor VIIa-tissue factor (K i ‫؍‬ 1.6 M), factor IXa (K i ‫؍‬ 206 nM), factor Xa (K i ‫؍‬ 364 nM), and factor XIIa (K i ‫؍‬ 430 nM). This specificity profile was to a large extent mimicked, albeit with reduced potency, by the individual Kunitz domains. As predicted from this in vitro specificity profile, recombinant placental bikunin (1-170) prolonged the clotting time in an activated partial thromboplastin time assay.Blood clotting, resulting either from the extrinsic pathway following tissue injury or the intrinsic pathway following contact activation, involves tightly regulated proteolytic cascades (1). The intrinsic pathway is initiated by activation of factor XII either through proteolysis or contact with negatively charged surfaces. Activated factor XIIa, in turn, converts plasma prekallikrein to kallikrein, which can then activate additional factor XII. Factor XIIa activates factor XI, which, in turn, activates factor IX. Activated factor IX forms a complex with factor VIIIa, phospholipid, and calcium, which converts factor X to factor Xa. Factor X is also activated by the factor VIIatissue factor complex operating within the extrinsic pathway. Thrombin generation by factor Xa in complex with factor Va leads ultimately to the formation of the fibrin clot. Thrombus formation is also regulated by the fibrinolytic system whereby plasmin, formed from plasminogen by the action of kallikrein, tissue plasminogen activator (tPA), 1 or urokinase, breaks down both fibrinogen and fibrin (2).Protease inhibitors play critical roles in the regulation of the coagulation and fibrinolytic systems. Tissue factor pathway i...

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“…The plasma contact system plays an important role in initiation of mammalian acute inflammatory responses following tissue injury (1,2). It is mainly composed of four plasma proteins, prekallikrein, factor XII, factor XI, and high molecular weight kininogen (HK).…”

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confidence: 99%

“…It is mainly composed of four plasma proteins, prekallikrein, factor XII, factor XI, and high molecular weight kininogen (HK). 1 Activation of the plasma contact system is initiated by binding of both factor XII and a prekallikrein-HK complex to a biological activating surface such as the endothelial cell surface and then is rapidly amplified by reciprocal activation of kallikrein and factor XII on this surface. Factor XII and HK binding to these surfaces requires Zn 2ϩ ions (3)(4)(5)(6), and Zn 2ϩ ions are thought to induce conformational change in both proteins (7)(8)(9).…”

mentioning

confidence: 99%

“…: 81-59-231-5013; Fax: 81-59-231-5215; E-mail: m-yuda@doc.medic.mie-u.ac.jp. 1 The abbreviations used are: HK, high molecular weight kininogen; D7r, D7-related protein; CTI, corn trypsin inhibitor; SBTI, soybean trypsin inhibitor; PC, phosphatidylcholine; PtdInsP, phosphatidylinositol phosphate; MBP, maltose binding protein; APTT, activated partial thromboplastin time; PT, prothrombin time; DS 500, dextran sulfate of molecular weight 500,000; ELISA, enzyme-linked immunosorbent assay; SPR, surface plasmon resonance; RU, resonance unit(s).…”

mentioning

confidence: 99%

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A Mosquito Salivary Protein Inhibits Activation of the Plasma Contact System by Binding to Factor XII and High Molecular Weight Kininogen

Isawa

Yuda

Orito

et al. 2002

Journal of Biological Chemistry

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The salivary glands of female mosquitoes contain a variety of bioactive substances that assist their bloodfeeding behavior. Here, we report a salivary protein of the malarial vector mosquito, Anopheles stephensi, that inhibits activation of the plasma contact system. This factor, named hamadarin, is a 16-kDa protein and a major component of the saliva of this mosquito. Assays using human plasma showed that hamadarin dose-dependently inhibits activation of the plasma contact system and subsequent release of bradykinin, a primary mediator of inflammatory reactions. Reconstitution experiments showed that hamadarin inhibits activation of the plasma contact system by inhibition of the reciprocal activation of factor XII and kallikrein. Direct binding assays demonstrated that this inhibitory effect is due to hamadarin binding to both factor XII and high molecular weight kininogen and interference in their association with the activating surface. The assays also showed that hamadarin binding to these proteins depends on Zn 2؉ ions, suggesting that hamadarin binds to these contact factors by recognizing their conformational change induced by Zn 2؉ binding. We propose that hamadarin may attenuate the host's acute inflammatory responses to the mosquito's bites by inhibition of bradykinin release and thus enable mosquitoes to take a blood meal efficiently and safely.

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Surface-mediated defense reactions. The plasma contact activation system.

Cited by 234 publications

References 51 publications

The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc‐dependent binding to an anionic surface

The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc‐dependent binding to an anionic surface

Characterization of Placental Bikunin, a Novel Human Serine Protease Inhibitor

A Mosquito Salivary Protein Inhibits Activation of the Plasma Contact System by Binding to Factor XII and High Molecular Weight Kininogen

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