Synthesis and release of Hageman factor (Factor XII) by the isolated perfused rat liver.

Abstract

A B S T R A C T The site of synthesis of Hageman factor (HF, Factor XII) has not been previously demonstrated with certainty. We have studied the production and release of HF in the isolated perfused rat liver and have compared rates of synthesis in this system with absolute rates of degradation measured in vivo. Rat livers, perfused for 5 h with a recycling fluid consisting of a perfluorochemical emulsion (Fluosol 43), were used to demonstrate a cumulative increase of HF in the perfusate as measured by a specific and sensitive radioimmunoassay. The rate of increase in the perfusate pool of HF during the final 4 h of perfusion yielded a mean synthetic rate of 3.5 Ag/h per 100 g body wt, which was -0.2% of the synthetic rate of albumin in the same system. The cumulative appearance of albumin and transferrin was linear after 1 h and calculated rates of synthesis were 2,012 tg/h per 100 g and 263 tsg/h per 100 g body wt, respectively.De novo synthesis of HF was confirmed by demonstrating incorporation of [14C]lysine into specific immunoprecipitates of HF, and by the observations that both specific incorporation of labeled amino acid and net release of immunoassayable HF were inhibited by the administration of cycloheximide. Finally, it was evident that the rates of synthesis observed in the isolated perfused liver agreed closely with absolute rates of degradation of HF measured in vivo with '25I-rat

Factor XII-induced mitogenesis is mediated via a distinct signal transduction pathway that activates a mitogen-activated protein kinase.

“…Factor XII is a liver-derived glycoprotein with procoagulant properties activated upon direct contact with subendothelial collagen. The amount of factor XII required to induce growth (3-6 ,ug/ml) is 1/6th-1/10th the normal titer of factor XII in plasma (35)(36)(37)(38)(39)(40) ,tg/ml) (22). Thus, the concentration of factor XII that promotes cell growth is much less than that required for induction of clotting in vitro.…”

“…Analysis of variance was used to evaluate the significance of differences between the experimental cultures and their controls (21 (35)(36)(37)(38)(39)(40) jig/ml) (22). The…”

“…(22). The concentration of EGF varies considerably among different tissues, ranging from about 0.2 to 60 ng/ml (5).…”

Adrenomedullary catecholamine, pressor and chronotropic responses to human coagulation β-FXIIa mediated by endogenous kinins

“…Importantly, it is only HMWK (the substrate for bradykinin release by prekallikrein) that participates in classic intrinsic blood coagulation. FXII titres in human or rat plasma are approximately 40 mg/ml [31,32]. In these bioassay autonomic-blocked Brown Norway rats, 1 mg/kg b-FXIIa, or approximately 0.05% of the total rat FXII zymogen content, evoked a 170-fold increase in arterial epinephrine concentrations.…”

Activated plasma coagulation β-Factor XII-induced vasoconstriction in rats

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