Human pancreatic duct cells exert tissue factor-dependent procoagulant activity: relevance to islet transplantation.
Activation of the coagulation cascade contributes to early graft loss and intraportal thrombotic events in clinical islet transplantation. Although these complications were shown to be related to the presence of tissue factor in human islet preparations, the contribution of duct cells, which represent a major contaminant of clinical islet isolates, has not been specified so far. Herein, we used flow cytometry, immunohistochemistry, RT-PCR, and functional coagulation assays to demonstrate that duct cells exert a potent factor VII-dependent procoagulant activity related to their expression of tissue factor. Both the classical membrane-bound and the recently described soluble form of tissue factor were shown to be synthesized by duct cells. We conclude that contaminating duct cells contribute to early beta-cell damage after islet transplantation through their involvement in tissue factor-mediated thrombotic and inflammatory events.
Beuneu
Claire
C
Laboratory of Experimental Immunology, Université Libre de Bruxelles, Hôpital Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium.
Vosters
Olivier
O
Movahedi
Babak
B
Remmelink
Myriam
M
Salmon
Isabelle
I
Pipeleers
Daniel
D
Pradier
Olivier
O
Goldman
Michel
M
Verhasselt
Valérie
V
D001780:Blood Coagulation Tests; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016381:Islets of Langerhans Transplantation; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000378:metabolism*
D013925:Thromboplastin