What question did this study set out to answer?

To identify the essential plasma components and proteolytic cleavage events governing dextran sulfate-induced prekallikrein activation.

June 1, 1982BloodOpen Access

The contact activation mechanism in human plasma: activation induced by dextran sulfate

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Authors

FGFedde van der GraafRadboud University Nijmegen FKFJ Keus RVRA VlooswijkScripps Health

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Implication

In vitro biochemical analysis demonstrates dextran sulfate-induced prekallikrein activation kinetics in human plasma, indicating essential cofactors in contact activation.

Key Points

To identify the essential plasma components and proteolytic cleavage events governing dextran sulfate-induced prekallikrein activation.
Incubated normal human plasma and plasmas deficient in factor XII, prekallikrein, or high molecular weight (HMW) kininogen with dextran sulfate at 4 °C for 7 minutes.
Assessed inhibition using specific antisera against prekallikrein and HMW kininogen.
Tracked proteolytic cleavage kinetics using radiolabeled 125I-prekallikrein, 131I-HMW kininogen, and 125I-factor XII analyzed by SDS-PAGE under reducing conditions.
Factor XII- and prekallikrein-deficient plasmas generated zero kallikrein activity, while HMW kininogen-deficient plasma produced only 8% activity, with specific antisera confirming their requirement for activation.
Generation of kallikrein activity matched the rapid proteolytic cleavage of prekallikrein and HMW kininogen, whereas factor XII cleavage occurred much more slowly and to a lesser extent.
Incubation with dextran sulfate initially produced alpha-factor-XIIa within the first minutes, followed by beta-factor-XIIa generation during prolonged incubation.

Cite This Study

Graaf et al. (1982) studied this question.

synapsesocial.com/papers/6a1896b4985da83d54918672 https://doi.org/10.1182/blood.v59.6.1225.1225

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Implication

In vitro biochemical analysis demonstrates dextran sulfate-induced prekallikrein activation kinetics in human plasma, indicating essential cofactors in contact activation.

The contact activation mechanism in human plasma: activation induced by dextran sulfate

Discussion

Member takes

Implication

Key Points

Cite This Study

The contact activation mechanism in human plasma: activation induced by dextran sulfate

Discussion

Member takes

Implication

Key Points

Cite This Study

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