Abstract
High levels of donor-derived high-mobility group box 1 (HMGB1) protein have been associated with poor islet graft outcome in mouse models. The aim of our work was to determine whether HMGB1 released by human islets had independent proinflammatory effects that influence engraftment in humans. Human islet preparations contained and released HMGB1 in different amounts, as determined by Western blot and ELISA (median 17 pg/ ml/IEQ/24 h; min-max 0-211, n = 74). HMGB1 release directly correlated with brain death, donor hyperamilasemia, and factors related to the pancreas digestion procedure (collagenase and digestion time). HMGB1 release was significantly positively associated with the release of other cytokines/chemokines, particularly with the highly released "proinflammatory" CXCL8/IL-8, CXCL1/GRO-α, and the IFN-γ-inducible chemokines CXCL10/IP-10 and CXCL9/MIG. HMGB1 release was not modulated by Toll-like receptor 2, 3, 4, 5, and 9 agonists or by exposure to IL-1β. When evaluated after islet transplantation, pretransplant HMGB1 release was weakly associated with the activation of the coagulation cascade (evaluated as serum cross-linked fibrin products), but not with the immediate posttransplant inflammatory response. Concordantly, HMGB1 did not affect short-term human islet function. Our data show that human islet HMGB1 release is a sign of "damaged" islets, although without any independent direct role in graft failure.
| Original language | English |
|---|---|
| Pages (from-to) | 2175-2186 |
| Number of pages | 12 |
| Journal | Cell Transplantation |
| Volume | 22 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2013 |
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Keywords
- Engraftment
- High-mobility group box 1 (HMGB1)
- Human
- Islet transplantation
ASJC Scopus subject areas
- Cell Biology
- Transplantation
- Biomedical Engineering
- Medicine(all)
Cite this
Human pancreatic islet preparations release HMGB1 : (Ir)relevance for graft engraftment. / Nano, Rita; Racanicchi, Leda; Melzi, Raffaella; Mercalli, Alessia; Maffi, Paola; Sordi, Valeria; Ling, Zhidong; Scavini, Marina; Korsgren, Olle; Celona, Barbara; Secchi, Antonio; Piemonti, Lorenzo.
In: Cell Transplantation, Vol. 22, No. 11, 2013, p. 2175-2186.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human pancreatic islet preparations release HMGB1
T2 - (Ir)relevance for graft engraftment
AU - Nano, Rita
AU - Racanicchi, Leda
AU - Melzi, Raffaella
AU - Mercalli, Alessia
AU - Maffi, Paola
AU - Sordi, Valeria
AU - Ling, Zhidong
AU - Scavini, Marina
AU - Korsgren, Olle
AU - Celona, Barbara
AU - Secchi, Antonio
AU - Piemonti, Lorenzo
PY - 2013
Y1 - 2013
N2 - High levels of donor-derived high-mobility group box 1 (HMGB1) protein have been associated with poor islet graft outcome in mouse models. The aim of our work was to determine whether HMGB1 released by human islets had independent proinflammatory effects that influence engraftment in humans. Human islet preparations contained and released HMGB1 in different amounts, as determined by Western blot and ELISA (median 17 pg/ ml/IEQ/24 h; min-max 0-211, n = 74). HMGB1 release directly correlated with brain death, donor hyperamilasemia, and factors related to the pancreas digestion procedure (collagenase and digestion time). HMGB1 release was significantly positively associated with the release of other cytokines/chemokines, particularly with the highly released "proinflammatory" CXCL8/IL-8, CXCL1/GRO-α, and the IFN-γ-inducible chemokines CXCL10/IP-10 and CXCL9/MIG. HMGB1 release was not modulated by Toll-like receptor 2, 3, 4, 5, and 9 agonists or by exposure to IL-1β. When evaluated after islet transplantation, pretransplant HMGB1 release was weakly associated with the activation of the coagulation cascade (evaluated as serum cross-linked fibrin products), but not with the immediate posttransplant inflammatory response. Concordantly, HMGB1 did not affect short-term human islet function. Our data show that human islet HMGB1 release is a sign of "damaged" islets, although without any independent direct role in graft failure.
AB - High levels of donor-derived high-mobility group box 1 (HMGB1) protein have been associated with poor islet graft outcome in mouse models. The aim of our work was to determine whether HMGB1 released by human islets had independent proinflammatory effects that influence engraftment in humans. Human islet preparations contained and released HMGB1 in different amounts, as determined by Western blot and ELISA (median 17 pg/ ml/IEQ/24 h; min-max 0-211, n = 74). HMGB1 release directly correlated with brain death, donor hyperamilasemia, and factors related to the pancreas digestion procedure (collagenase and digestion time). HMGB1 release was significantly positively associated with the release of other cytokines/chemokines, particularly with the highly released "proinflammatory" CXCL8/IL-8, CXCL1/GRO-α, and the IFN-γ-inducible chemokines CXCL10/IP-10 and CXCL9/MIG. HMGB1 release was not modulated by Toll-like receptor 2, 3, 4, 5, and 9 agonists or by exposure to IL-1β. When evaluated after islet transplantation, pretransplant HMGB1 release was weakly associated with the activation of the coagulation cascade (evaluated as serum cross-linked fibrin products), but not with the immediate posttransplant inflammatory response. Concordantly, HMGB1 did not affect short-term human islet function. Our data show that human islet HMGB1 release is a sign of "damaged" islets, although without any independent direct role in graft failure.
KW - Engraftment
KW - High-mobility group box 1 (HMGB1)
KW - Human
KW - Islet transplantation
UR - http://www.scopus.com/inward/record.url?scp=84884586957&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884586957&partnerID=8YFLogxK
U2 - 10.3727/096368912X657783
DO - 10.3727/096368912X657783
M3 - Article
C2 - 23051559
AN - SCOPUS:84884586957
VL - 22
SP - 2175
EP - 2186
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 11
ER -