Activation of Hageman Factor in Solid and Fluid Phases

Abstract

The activation of Hageman factor results from its exposure to various insoluble particles having negative charges on their surfaces, such as glass, kaolin, extracellular membranes, etc., and to enzymes such as trypsin in solution. We have currently found that activation of Hageman factor by kaolin is highly inefficient in the presence of plasma, only a small percentage of the Hageman factor being utilized in the reaction (1). This led to the speculation that important soluble activators may exist in plasma that could greatly amplify the activation. Such activators could be released from cells at the moment of injury of tissues while others could be activated in the plasma. From previous data enzymes would comprise likely candidates for activators in the fluid phase, and one might reasonably suspect the involvement of those enzymes activated under the same circumstances as Hageman factor. One such enzyme, plasmin, has been shown to activate Hageman factor (2), a finding that was subsequently confirmed (3). A similar capacity of two other enzymes, kallikrein and clotting Factor XI (plasma thromboplastin antecedent, PTA) 1, both of which are activated directly by Hageman factor, is described herein. A key role of kallikrein was observed in amplifying the activation of Hageman factor which is essential for an adequate rate of generation of the fibrinolytic and intrinsic clotting systems.We will also report upon changes observed in the structure of Hageman factor incurred during activation in fluid phase by plasma enzymes and in solid phase by insoluble, negatively charged particles in the absence of detectable enzymes. The data form a base for understanding the mechanisms of Hageman factor activation in pathologic conditions. * This work was supported by U. S. Public Health Service Grant AI-07007, the American Heart Association, and the Council for Tobacco Research.:~ Recipient of U. S. Public Health Service Research Career Development Award 1 KO4 AM 40086-02.1 Abbreviations used in this paper: AGLME, acetyl-glycine-lysine methyl ester; BAEe, benzoyl-n-arginine ethyl ester; BSA, bovine serum albumin; DFP, diisopropyl fluorophosphate; EACA, e-amino-n-caproic acid; OMTI, Ovomucoid trypsin inhibitor; PMSF, phenyl methyl sulfonyl fluoride; PTA, plasma thromboplastin antecedent; SDS, sodium dodecyl sulfate; TBS, 0.01 M tris(hydroxymethyl)aminomethane buffer pH 7.4 in 0.15 M NaCI.

An Objective Examination for Painful Hip After Total Hip Arthroplasty

“…Thus, it is considered that the kallikrein activity in plasma mainly reflects the micromotion of the prosthesis in the radiolucent zone. Exposure of collagen fibres in fibrous tissue of the radiolucent zone (DeLee & Charnley 1976), resulting from micromotion, may also participate as an inducer in contact activation (Cochrane et al 1973).…”

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

“…Furthermore, damage to the EC layer might expose subcellular structures with a sufficient density of negative charges to facilitate assembly of the surfacebound HF-high Mr kininogen-Factor XI-prekallikrein complexes similar to the one demonstrated for kaolin (12,39,40). Under these circumstances, the EC enzyme could initiate HF cleavage, an essential step for the reciprocal activation between HF and prekallikrein (41). This may be one mechanism by which HF is activated in vivo.…”

The Role of Bradykinin System in Type 2 Diabetes

“…Higher concentrations of prekallikrein levels may suggest the onset of renal abnormalities. In fact, high plasma prekallikrein levels have been documented in type 1 diabetic patients [27]. These investigators suggested that increased plasma prekallikrein level could be a risk factor for hypertension and nephropathy in type 1 diabetes.…”

“…Tissue kallikrein has also been reported to be present in plasma [22,23] Plasma kallikrein preferentially acts on high molecular weight kininogen substrate to release BK. BK promotes both cardiovascular and renal functions, for example, vasodilation, naturesis and diuresis [24,25] BK is rapidly (< 15 sec) inactivated by circulating kinases [26] BK acts on B1receptor (B1R) and B2 receptor (B2R) [27] to elicit physiological and pharmacological actions. It has been shown previously that type 1 diabetic patients are at a risk of developing nephropathy, having increased renal tissue kallikrein and BK levels [28].…”