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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

Johansson, H; Lukinius, A; Moberg, L; Lundgren, T; Berne, C; Foss, A; Felldin, M; Källén, Ragnar LU ; Salmela, K and Tibe, A, et al. (2005) In Diabetes 54(6). p.1755-1762
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... (More)
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. (Less)
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Contribution to journal
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published
subject
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Diabetes
volume
54
issue
6
pages
1755 - 1762
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000229499600017
  • pmid:15919797
  • scopus:20044371024
ISSN
1939-327X
language
English
LU publication?
yes
id
d20b245a-58d3-4d5a-828e-e4e0d1fa3f79 (old id 895390)
alternative location
http://diabetes.diabetesjournals.org/cgi/content/full/54/6/1755
date added to LUP
2008-01-16 11:47:39
date last changed
2017-11-12 04:04:16
@article{d20b245a-58d3-4d5a-828e-e4e0d1fa3f79,
  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.},
  author       = {Johansson, H and Lukinius, A and Moberg, L and Lundgren, T and Berne, C and Foss, A and Felldin, M and Källén, Ragnar and Salmela, K and Tibe, A and Tufveson, G and Ekdahl, KN and Elgue, G and Korsgren, O and Nilsson, B},
  issn         = {1939-327X},
  language     = {eng},
  number       = {6},
  pages        = {1755--1762},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation},
  volume       = {54},
  year         = {2005},
}