We have previously reported on the presence of
proenzymes and inhibitors of the contact system in ascitic fluid.
Malignancy-related
ascites was also found to contain both high and
low molecular weight kininogen (HK and LK). On this basis we have studied a possible activation of the contact system in
ascites. Generation of amidolytic activity towards the
chromogenic substrate S-2302 after incubation with
dextran sulphate (DXS), was found in
ascites from patients with
gastrointestinal cancer, but not in
ascites from patients with benign
liver disease. It is concluded that
malignancy-related
ascites allows contact activation to take place, while benign
ascites does not. This activation process, generating
bradykinin, could possibly be of relevance to the mechanism of
ascites generation. Plasma samples from patients with
ascites were also tested in relation to activation of the contact system. Activation was evaluated by immunoblotting, studying the disappearance of intact HK after the initiation of activation with different concentrations of DXS. In control plasma, activation took place at low concentrations of DXS (25 - 50 micrograms/ml). In plasma samples from patients with
malignancy-related or benign
ascites, contact activation was depressed. In some samples concentrations of DXS up to 1 mg/ml, were not able to activate the contact system at all. Concentrations of
proenzymes and relevant inhibitors in the contact system, HK and total
protein were also determined. We found the concentration of
prekallikrein to be positively correlated with the degree of activation. Concentrations of inhibitors such as C1-inhibitor, did not show any correlation with activation.