EFFECT OF PORCINE ENDOTHELIAL TISSUE FACTOR PATHWAY INHIBITOR ON HUMAN COAGULATION FACTORS1
作者:
Kopp2 Christoph,
Siegel2 Jonathan,
Hancock2 Wayne,
Anrather2 Josef,
Winkler2 Hans,
Geczy3 Carolyn,
Kaczmarek2 Elzbieta,
Bach2 Fritz,
Robson2,4 Simon,
期刊:
Transplantation
(OVID Available online 1997)
卷期:
Volume 63,
issue 5
页码: 749-758
ISSN:0041-1337
年代: 1997
出版商: OVID
数据来源: OVID
摘要:
Background.Delayed xenograft rejection (DXR) is characterized by inflammation and vascular thrombosis. Activation of coagulation may occur as a result of tissue factor (TF) expression on both activated donor endothelial cells (EC) and recipient infiltrating monocytes (Mo). In addition, natural anticoagulants associated with porcine endothelial cells may not function adequately across species.Methods.In the present study, we examined the interaction of the TF pathway of coagulation with the natural anticoagulant TF pathway inhibitor, in xenogeneic leukocyte-EC cultures in vitro, and during rejection of discordant xenografts in vivo.Results.Coculture of human Mo with pig aortic EC (PAEC) resulted in 1.7-fold and 2-fold higher induction of Mo TF and Mo intercellular adhesion molecule-1, respectively, when compared with coculture with human aortic endothelial cells (HAEC). In addition, TF-dependent and -independent activation of coagulation factor X was higher on PAEC than on HAEC. Low levels of mRNA for tissue factor pathway inhibitor (TFPI) and its variant, TFPI-2, in resting PAEC were up-regulated by stimulation with tumor necrosis factor α. Procoagulant activity of recombinant human TF complexed to activated factor VII was inhibited by PAEC and HAEC-associated TFPI by 22% and 56%, respectively. In contrast, human activated factor X (factor Xa) activity was inhibited by human, but not porcine, EC-associated TFPI, suggesting functional incompatibility of PAEC for human factor Xa. Endothelial TFPI was detected in pig control organs and after hyperacute rejection, but was lost from the vasculature during DXR.Conclusions.Lack of appropriate human factor Xa inhibition by porcine EC during hyperacute rejection and loss of porcine EC TFPI during DXR could promote the development of a procoagulant environment leading to xenograft rejection.
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