Detection and Quantitation of Cleaved and Uncleaved High Molecular Weight Kininogen in Plasma by Ligand Blotting with Radiolabeled Plasma Prekallikrein or Factor XI

Bernhard Lämmle; Bruce L Zuraw; Mary Jo Heeb; Hans Peter Schwarz; Mauro Berrettini; John G Curd; John H Griffin

doi:10.1055/s-0038-1642745

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1988; 59(02): 151-161
DOI: 10.1055/s-0038-1642745

Original Articles

Schattauer GmbH Stuttgart

Detection and Quantitation of Cleaved and Uncleaved High Molecular Weight Kininogen in Plasma by Ligand Blotting with Radiolabeled Plasma Prekallikrein or Factor XI

Bernhard Lämmle

^*Coagulation Laboratory, Central Hematology Laboratory, University of Bern, Inselspital, 3010 Bern, Switzerland

,

Bruce L Zuraw

^�The Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, CA, USA

,

Mary Jo Heeb

The Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA, USA

,

Hans Peter Schwarz

⁺Department of Medicine, University of Vienna, Vienna, Austria

,

Mauro Berrettini

The Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA, USA

,

John G Curd

^�The Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, CA, USA

,

John H Griffin

The Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA, USA

› Author Affiliations

Abstract

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Summary

A method for the quantitative assay of native single chain and kallikrein cleaved two-chain high molecular weight (HMW)-kininogen in plasma is described. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of whole plasma is followed by electrotransfer of the electropherogram to nitrocellulose membranes and detection of the blotted HMW-kininogen with its physiologic ligands, radiolabeled plasma prekallikrein or radiolabeled factor XI. Using unreduced SDS-PAGE cleaved two-chain HMW-kininogen (Mr ∼107,000 and 95,000), is elec-trophoretically separated from uncleaved single chain HMW-kininogen (Mr ∼150,000). Counting the radioactivity of the nitrocellulose pieces corresponding to cleaved HMW-kininogen permits its quantitative measurement by comparison with standards consisting of decreasing amounts of fully dextran sulfate activated normal human plasma. Single chain HMW-kininogen is similarly assayed using reduced SDS-PAGE and unactivated normal human plasma standards.

This technique is highly specific and sensitive to about 50 ng of either cleaved or uncleaved HMW-kininogen. Varying amounts of cleaved HMW-kininogen were found in a small series of plasmas from patients suffering from various inflammatory conditions. Higher levels of in vivo cleaved HMW-kininogen were observed during acute attacks of hereditary angioedema due to Cl-inhibitor deficiency. This technique may be useful for the assessment of the degree of in vitro or in vivo activation of the contact system.

Keywords

High molecular weight kininogen - Proteolytic cleavage - Ligand blotting - Contact activation system

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References

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