Summary
The contribution of the various components of the contact system in the generation
of factor XIIa (FXIIa) and of kallikrein (KRN) on an electronegative surface and the
release of the generated enzymes to the bulk phase was examined in mixtures of normal
human plasma and plasmas congenitally deficient in these components. The incubation
of normal human plasma in the presence of sulphatide vesicles (40 μM) resulted in
a fast generation of amidolytic activities due to FXIIa and to KRN followed by slower
first-order inactivation rates of FXIIa (k’FXIIa ) and of KRN (k’KRN ) due to the presence of esterase inhibitors. Variation of the levels of factor XII
(FXII), over a wide range, showed little effect on levels of FXIIa and of KRN but
no activities were detected in 100% FXII-deficient plasma. The variation of prekallikrein
(PKRN) concentration showed little effect on the generation of FXIIa but the generation
of KRN declined linearly with the decrease in the level of PKRN. No activities were
detected on treatment of PKRN-deficient plasma. The variation in the concentration
of high molecular weight kininogen (HK) showed effects on FXIIa and KRN that were
qualitatively similar to those seen on variation of PKRN but 100% HK-deficient plasma
generated considerable activities of both FXIIa and KRN. The variation in the concentration
of factor XI (FXI) showed no effect on the generation of FXIIa, whereas KRN levels
increased linearly with the contribution of FXI-deficient in normal plasma. The present
results suggest that the contiguous binding of FXIIa, FXII, PKRN-HK and FXI-HK onto
the electronegative surface induces a rapid generation of FXIIa and KRN. The bound
PKRN-HK complex prevents the release of generated FXIIa and therefore further binding
and activation of FXII from the bulk phase. Consequently, the turnover of FXII is
independent of its levels in the bulk phase and is rather related to the concentration
of contact surface. The generated KRN is also protected by HK. However, since the
enzyme responsible for the activation of PKRN-HK is FXIIa, the levels of generated
KRN are positively related to the concentration of substrate.
Keywords Contact activation - factor XII - prekallikrein - high molecular weight kininogen
- regulation of activation