Role of surface in surface-dependent activation of Hageman factor (blood coagulation Factor XII)

Abstract

The mechanism by which negatively charged substances such as celite, kaolin, or ellagic acid contribute to the surface-dependent activation of Hageman factor (Factor XII) was studied. Kinetic studies of the proteolytic activation of '514-labeled human Hageman factor by human plasma kallikrein, plasmin, activated Factor XI, and trypsin were performed in the presence and absence of hig molecular, weight kininogen and surface materials such as celite, kaolin, or ellagic acid. The results showed that surface-bound Hageman factor was 500 times more susceptible than soluble Hageman factor to proteolytic activation by kallikrein in the presence of high molecular weight kininogen. Surface binding of Hageman factor enhanced its cleavage by plasmin, activated Factor XI, and trypsin by 100-fold, 30-fold, and 5-fold, respectively. On a molar basis, trypsin was twice as potent as kallikrein in the cleavage of the surface-bound Hageman factor, while plasmin and activated Factor XI were an order of magnitude less potent than kallikrein. Kallikrein even at concentrations as low as 0.5 nM (i.e., 1/1000th of the concentration of prekallikrein' in plasma) was very potent in the limited proteolysis of the surface-boulid Hageman factor. These results suggest that substances classically known as "activating surfaces" promote the activation of Hageman factor indirectly by alerng its structure such that it is much more susceptible to proteolytic activation by otherplasma or cellular proteases.

Alkali treatment of microrough titanium surfaces affects macrophage/monocyte adhesion, platelet activation and architecture of blood clot formation

“…Since all cascades of blood coagulation are highly interlinked and proceed in a sequential manner, also contact activation of the intrinsic blood-clotting cascade induced by the cleavage of prekallikrein to kallikrein might be induced after implant implantation. Moreover, complement activation and the activation of platelets and leukocytes on an implant surface has been described extensively (Griffi n, 1978;Smith et al, 2003;Jackson, 2007). The chemistry and topography of the medical implant surfaces were demonstrated to be able to infl uence interactions with all blood components (Smith et al, 2003;Gorbet and Sefton, 2004).…”

Initiation of contact system activation in plasma is dependent on factor XII autoactivation and not on enhanced susceptibility of factor XII for kallikrein cleavage

“…not autoactivate but rather undergoes a conformational change that enhances its susceptibility for cleavage by kallikrein (Griffin, 1978;Rosing et al, 1985). According to this 'susceptibility' hypothesis, initiation of the contact system is dependent on the capability of a surface to induce conformational changes in FXII, as well as on the presence of traces of active kallikrein in plasma, possibly resulting from autoactivation of prekallikrein (Tans et al, 1987).…”

Activation of Rabbit Hageman Factor by Homogenates of Cultured Rabbit Endothelial Cells

“…Because diisopropylfluorophosphate abolished HF cleavage by the EC homogenate, it appears that a serine protease is responsible for this activity. Surface binding of HF renders it much more susceptible to cleavage by a number of enzymes (34). Because neither Triton X-100 nor hexadimethrine bromide (Polybrene) diminished the HF-cleaving activity of the cell homogenate, and because kaolin enhanced this activity, it seems unlikely that the presence of negatively charged material in the cell homogenate rendered HF more susceptible to enzymatic cleavage.…”