Activation of Factor XII in Plasma from Rats Pretreated with Tranexamic Acid. Inhibition of a Plasmin‐induced Loss of the Functional Activity of High Molecular Weight Kininogen

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Normal levels of factor XI1 and of high and low molecular weight kininogens (HMWK and LMWK) were registered in plasma specimens from 5 individuals who had developed anaphylactoid reactions upon injection of dextran during surgery (dextran reactors, DR). Factor XI1 was assayed as prekallikrein activator (PKA) activated with kaolin at 0 ' . and kininogen fractions were estimated through the release of kinin caused by plasma kallikrein or hog pancreas kallikrein (HPK). Subnormal levels of factor XI1 apparently present in plasma from one DR, and after affinity chromatography on a lysine-Sepharose column also in plasma from another DR, were normalized by addition of plasma deficient in factor XI1 or by addition of purified HMWK.Treatment of plasma from DR with acetone ( 2 5 % v/v) induced a conversion of HMWK into a state which was non-functional as a cofactor in the surface-dependent activation of factor XII, and the passage of plasma from DR through a lysine-Sepharose column altered the HMWK present to a substance that released kinin only very slowly by incubation with HPK. It is concluded that the treatments mentioned will favour the activation in plasma from DR of a factor that will cause the conversion of HMWK. Previous experiments with rat plasma demonstrated that plasmin and also a plasmin-like factor without affinity for lysine-Sepharose were able to destroy the capacity of HMWK to function as a cofactor in the surface-dependent activation of factor XII, without a corresponding release of kinin.

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Dextran‐Induced Anaphylactoid Reaction in Man: Altered Reactivity of High Molecular Weight Kininogen

Briseid

1980

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Activation of Factor XII in Rat Plasma: Protection by Benzamidine of the Cofactor Function of High Molecular Weight Kininogen

Briseid

Johansen

1981

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Factor XII has been assayed as kaolin‐activated prekallikrein activator in rat citrated plasma pretreated with acetone (Briseid et al. 1978 & 1979; Briseid & Berstad 1979). In the present work benzamidine added during blood collection increased the extent of activation by a factor of 6. Rat high molecular weight kininogen (HMWK) added to acetone‐treated citrated plasma likewise increased the activation, providing evidence of the protection by benzamidine of the cofactor function of HMWK. All cofactor capacity was retained after the removal of the kinin part of HMWK. Experiments carried out with plasminogen‐free plasma showed that plasmin could hardly be the factor responsible for the destruction of HMWK. The stoichiometric factor XII concentration‐effect curve obtained by diluting acetone‐treated rat plasma with acetone‐treated human factor XII deficient plasma showed that factor XII is present in functional excess, the concentration of HMWK deciding the extent of activation. By diluting acetone‐treated rat plasma with buffer, HM WK concentration‐effect curves were obtained which were approximately linear over a range of 0.03–0.40 μg (bradykinin equivalents) per ml kaolin incubate. No further activation of factor XII was obtained at 0.80 μg/ml.

Effect of Serotonin Antagonists on the Dextran‐induced Anaphylactoid Reaction in the Rat

Berstad

1981

Dextran injected intravenously into rats causes a rapid lowering of the extent of activation of factor XII and of the plasma levels of prekallikrein and plasminogen, and at the same time a profound fall in blood pressure. The effects on these dextran‐induced reactions of three serotonin antagonistic lysergic acid derivatives were studied in the rat: bromolysergic acid diethylamide (BOL 148), methysergide, and ergotamine. BOL 148 was found to be the only effective inhibitor of the blood pressure fall, possessing an inhibitory effect over the dose range 1.0–4.0 mg/kg intravenously. The finding supports the assumption that part of the dextran‐induced blood pressure fall is mediated by serotonin through D‐receptors. All three serotonin antagonists showed a serotonin‐like lowering effect on the activation of factor XII and on the level of prekallikrein in plasma (BOL 148 1.0–4.0 mg/kg; methysergide 0.10–0.60 mg/kg; ergotamine 0.10–0.60 mg/kg). The results with the serotonin antagonists alone and in combination with dextran provided evidence that the serotonin‐mediated part of the blood pressure fall can not be secondary to the effect of dextran on the plasma parameters assayed.