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Tissue Factor Produced by the Endocrine Cells of the Islets of Langerhans Is Associated With a Negative Outcome of Clinical Islet Transplantation
- Source :
- Diabetes. 54:1755-1762
- Publication Year :
- 2005
- Publisher :
- American Diabetes Association, 2005.
-
Abstract
- There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low–molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15–60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.
- Subjects :
- Adult
Male
medicine.medical_specialty
Time Factors
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Antithrombin III
Islets of Langerhans Transplantation
Enteroendocrine cell
Factor VIIa
Biology
Glucagon
Thromboplastin
Islets of Langerhans
Tissue factor
Internal medicine
Internal Medicine
medicine
Humans
Inflammation
geography
geography.geographical_feature_category
Insulin
Middle Aged
Islet
Immunohistochemistry
In vitro
Transplantation
Alternative Splicing
Endocrinology
Female
Peptide Hydrolases
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....42df6485b9e027afd78a27feaee17ad3
- Full Text :
- https://doi.org/10.2337/diabetes.54.6.1755