Human pancreatic islet preparations release HMGB1: (Ir)relevance for graft engraftment

Rita Nano, Leda Racanicchi, Raffaella Melzi, Alessia Mercalli, Paola Maffi, Valeria Sordi, Zhidong Ling, Marina Scavini, Olle Korsgren, Barbara Celona, Antonio Secchi, Lorenzo Piemonti

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish
Pages (from-to)2175-2186
Number of pages12
JournalCell Transplantation
Volume22
Issue number11
DOIs
Publication statusPublished - 2013

Fingerprint

Islets of Langerhans
Grafts
Transplants
Coagulation
Brain
Chemical activation
Digestion
Proteins
Toll-Like Receptor 3
Chemokine CXCL10
HMGB1 Protein
Toll-Like Receptor 2
Islets of Langerhans Transplantation
Brain Death
Collagenases
Fibrin
Interleukin-8
Interleukin-1
Chemokines
Pancreas

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 journalArticle

Nano, Rita ; Racanicchi, Leda ; Melzi, Raffaella ; Mercalli, Alessia ; Maffi, Paola ; Sordi, Valeria ; Ling, Zhidong ; Scavini, Marina ; Korsgren, Olle ; Celona, Barbara ; Secchi, Antonio ; Piemonti, Lorenzo. / Human pancreatic islet preparations release HMGB1 : (Ir)relevance for graft engraftment. In: Cell Transplantation. 2013 ; Vol. 22, No. 11. pp. 2175-2186.
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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

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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.

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