Studies on human plasma C1 inactivator-enzyme interactions. I. Mechanisms of interaction with C1s, plasmin, and trypsin.

Harpel, Peter C.; Cooper, Neil R.

doi:10.1172/jci107967

Cited by 207 publications

(85 citation statements)

References 42 publications

(26 reference statements)

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“…Cl-inhibitor, a plasma protein with a very high amount of carbohydrates (34% by wt, 17% of which is sialic acid) is composed of a single polypeptide chain ofM r 105 000 [1][2][3][4]. It inhibits a variety of enzymes of the complement system as well as others (e.g., plasmin, kallikrein, Hageman factor).…”

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Size and shape of human CI‐inhibitor

1981

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Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Size and shape of human CI‐inhibitor

1981

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“…Conflicting analytic gel studies have been published concerning the interaction of purified Cl-Inh and Cis. Some studies do show evidence of proteolytic degradation of the inhibitor concomitant to the formation of stable complexes on SDS-PAGE (24,55,57), whereas others do not (23,25,26,53). Moreover, studies that have demonstrated proteolysis of Cl-Inh by Cis disagree whether cleavage is enhanced (24) in the presence of heparin or not (57).…”

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

confidence: 99%

“…Cl-Inh is the only known inhibitor in plasma of activated Clr and Cls, components of the classical pathway of complement (18), and the major inhibitor of activated Factor XII (Hageman factor) and kallikrein of the contact pathway of coagulation (19)(20)(21)(22). Inhibition of these so-called target proteinases by functional Cl-Inh comprises both proteolytic cleavage of a substrate-like peptide bond in the reactive center of the inhibitor and covalent linkage of the proteinase to the inhibitor: formation of bimolecular proteinase-C1-Inh complexes (18,20,(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

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.

137

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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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“…Further, the esterase activity of plasmin is only slightly inhibited by a.2 macroglobulin (Ganrot, *1967b). The inhibition of plasmin by a2 macroglobulin (Ganrot, 1967b;Miillertz, 1972Miillertz, , 1974, antithrombin III (a2 protein) (Highsmith & Rosenberg, 1974) al anti-trypsin (Hercz, 1974 and Cl-esterase inhibitor (a2 protein) (Harpel & Cooper, 1975 …”

Section: Other Inhibitors In the Crude Preparationmentioning

confidence: 99%

The primary inhibitor of plasmin in human plasma

Müllertz

Clemmensen

1976

Biochemical Journal

269

123

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A complex between plasmin and an inhibitor was isolated by affinity chromatography from urokinase-activated human plasma. The complex did not react with antibodies against any of the known proteinase inhibitors in plasma. A rabbit antiserum against the complex was produced. It contained antibodies against plasminogen+plasmin and an a2 protein. By crossed immunoelectrophoresis the a2 protein was shown to form a complex with plasmin, when generated by urokinase in plasma, and with purified plasmin. The a2 protein was eluted by Sephadex G-200 gel filtration with KD approx. 0.35, different from the other inhibitors of plasmin in plasma, and corresponding to an apparent relative molecular mass (Mr) of about 75000. By sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the Mr of the complex was found to be approx. 130000. After reduction of the complex two main bands of protein were observed, with Mr about 72000 and 66000, probably representing an acyl-enzyme complex of plasmin-light chain and inhibitorheavy chain, and a plasmin-heavy chain. A weak band with Mr 9000 was possibly an inhibitor-light chain. The inhibitor was partially purified and used to titrate purified plasmin of known active-site concentration. The inhibitor bound plasmin rapidly and strongly. Assuming an equimolar combining ratio, the concentration of active inhibitor in normal human plasma was estimated to be 1.1 umol/l. A fraction about 0.3 of the antigenic inhibitor protein appeared to be functionally inactive. In plasma, plasmin is primarily bound to the inhibitor. Only after its saturation does lysis of fibrinogen and fibrin occur and a complex between plasmin and a2 macroglobulin appear.

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Studies on human plasma C1 inactivator-enzyme interactions. I. Mechanisms of interaction with C1s, plasmin, and trypsin.

Abstract: A B S T R A C T This study has

Cited by 207 publications

References 42 publications

Size and shape of human CI‐inhibitor

Size and shape of human CI‐inhibitor

Proteolytic inactivation of plasma C1- inhibitor in sepsis.

The primary inhibitor of plasmin in human plasma

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