Intrinsic plasma fibrinolysis: Involvement of urokinase-related activity in the factor XII-independent plasminogen proactivator pathway

article


Kluft, C.

Wijngaards, G.

Jie, A.F.H.
A portion of human blood fibrinolytic activity can be quenched by antibodies to urokinase. We attempted to identify this portion and its position in the three pathways (extrinsic, intrinsic factor XII dependent, and intrinsic factor XII independent) of plasminogen activator activity that have been defined in the DEFs of plasma. Activity quenching in various plasmas (including plasma adsorbed by agarose-bound AUK) demonstrated the involvement of a discrete activator activity of 40 to 50 BAU/ml with little variation among individuals (43 ?? 6 (SD) BAU/ml, n = 13). The quenching did not involve, quantitatively or qualitatively, the extrinsic (tissue-type) plasminogen activator activity varying between 1 and 146 BAU/ml in baseline plasma and in plasma obtained after stimulation by venous occlusion, exercise, or DDAVP administration. In confirmation, extrinsic activator activity was recovered in plasma adsorbed by agarose-bound AUK. The quenching also did not involve the factor XII-dependent activities; it was quantitatively normal in plasma with Hageman (n = 3) and Fletcher (n = 2) traits, and AUK did not interfere with the generation of factor XII-dependent fibrinolytic activity by addition of purified activated factor XII in plasma with Hageman trait. There was no effect of AUK on kallikrein generation, kallikrein activities, or the APPT, nor were these aspects altered in depleted plasma. In conclusion, the quenching involved the factor XII-independent system of intrinsic fibrinolysis. Addition of purified urinary urokinase did not result in restoration of missing activity in plasma adsorbed by AUK-agarose. The quenching, therefore, probably involved an apparent urokinase-related activator component in plasma.
Chemicals/CAS: blood clotting factor 12, 9001-30-3; desmopressin, 16679-58-6; urokinase, 139639-24-0; Dextran Sulfate, 9042-14-2; Dextrans, 9004-54-0; Enzyme Precursors; Immune Sera; Plasminogen Activators, EC 3.4.21.-; plasminogen proactivator; Serum Globulins; Urinary Plasminogen Activator, EC 3.4.21.73
Topics























antibodyblood clotting factor 12desmopressinurokinaseblood and hemopoietic systemblood clotting factor 12 deficiencydose responsedrug mechanismdrug responsefibrinolysishumanhuman cellplasminogen activator antibodyplasminogen proactivatorDextran SulfateDextransEnzyme PrecursorsFibrinolysisHumanImmune SeraPlasminogen ActivatorsSerum GlobulinsSupport, Non-U.S. Gov'tUrinary Plasminogen Activator
TNO Identifier
229603
Repository link
https://resolver.tno.nl/uuid:e513db6b-c5ed-4a0a-ac4e-ca735b2341e7
ISSN
00222143
Source
Journal of Laboratory and Clinical Medicine, 103(3), pp. 408-419.
Pages
408-419
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