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Thromb Haemost 1998; 79(03): 529-538
DOI: 10.1055/s-0037-1614939
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Regulation of Monocyte Tissue Factor Activity by Allogeneic and Xenogeneic Endothelial Cells

Christoph W. Kopp
1   From the Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; and The Heart Research Institute, Camperdown, Australia
,
Simon C. Robson
1   From the Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; and The Heart Research Institute, Camperdown, Australia
,
Jonathan B. Siegel
1   From the Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; and The Heart Research Institute, Camperdown, Australia
,
Josef Anrather
1   From the Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; and The Heart Research Institute, Camperdown, Australia
,
Hans Winkler
1   From the Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; and The Heart Research Institute, Camperdown, Australia
,
Shane Grey
1   From the Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; and The Heart Research Institute, Camperdown, Australia
,
Elzbieta Kaczmarek
1   From the Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; and The Heart Research Institute, Camperdown, Australia
,
Fritz H. Bach
1   From the Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; and The Heart Research Institute, Camperdown, Australia
,
Carolyn L. Geczy
1   From the Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; and The Heart Research Institute, Camperdown, Australia
› Author AffiliationsThis work was supported by grants from Sandoz Pharma, Basel, Switzerland and the National Health and Medical Research Council of Australia. C. W. K. holds a “Max Kade” fellowship from the Austrian Academy of Science. S. C. R. had support from the Medical Research Council Liver Center, University of Cape Town, South Africa.
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Publication History

Received 27 January 1997

Accepted after resubmission 27 October 1997

Publication Date:
07 December 2017 (online)

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Summary

The regulation of tissue factor (TF) activity by the cell associated tissue factor pathway inhibitor (TFPI) during monocyte (Mo) and endothelial cell (EC) interactions is not fully understood. This report describes co-ordinate induction of TF antigen (TF-Ag) and membrane-associated TFPI-Ag on human Mo following coculture with human aortic (HAEC) or porcine aortic EC (PAEC) or after stimulation with TNFα. We show that both allo- and xenogeneic EC induce human Mo-TF antigen in short-term culture. However, the TF activity of TNFα-primed Mo is suppressed when these cells are cocultured with HAEC [by 40.3 ± 6.3% (p <0.02)] or PAEC [by 50.5 ± 10.6% (p <0.001)]. Antibody (Ab) blocking studies confirm that TFPI is the principal anticoagulant associated with this suppression of TF-activity. Our data indicate that anti-TF activity originates, at least in part, from the activated human Mo in the coculture; additionally, specific generation of TFPI by Mo is observed under the xenogeneic culture conditions. As Mo associated TF, induced by allo- or xenogeneic EC interactions, is regulated by cell-associated TFPI, we propose that infiltrating Mo may modulate the thrombotic process at sites of vascular injury in association with both allo- and xenograft rejection.

Aspects of the work were presented at the American Society for Hematology meeting in Orlando, FL, December 1996.