Role of CCL2/MCP-1 in islet transplantation

Raffaella Melzi, Alessia Mercalli, Valeria Sordi, Elisa Cantarelli, Rita Nano, Paola Maffi, Giovanni Sitia, Luca G. Guidotti, Antonio Secchi, Ezio Bonifacio, Lorenzo Piemonti

Research output: Contribution to journalArticlepeer-review

Abstract

High levels of donor-derived CCL2 have been associated with poor islet allograft outcome in patients with type 1 diabetes. The aim of our work was to determine whether CCL2 secreted by the islet has independent proinflammatory effects that influence engraftment and graft acceptance. Both in mice and humans CCL2 is significantly positively associated with other cytokines/chemokines, in particular with the highly released "proinflammatory" IL-6 and CXCL8 or CXCL1. Transplantation of CCL2-/- islets into syngenic recipients did not improve the transplant function. Transplantation of islets into CCL2-/- syngenic recipients led to a significant improvement of transplant function and partial abrogation of local hepatic inflammation. When evaluated in human islets CCL2 release was strongly related to the immediate local inflammatory response in the liver and impacted short-term human islet function dependently by the induced inflammatory response and independently by the immunosuppressive therapy. The data showed that islet CCL2 release is a sign of "inflamed" islets without having a direct role in graft failure. On the other hand, a causal effect for developing detrimental proinflammatory conditions after transplant was proved for recipient CCL2. Strategies to selectively decrease recipient, but not donor, CCL2 release may increase the success of islet transplantation.

Original languageEnglish
Pages (from-to)1031-1046
Number of pages16
JournalCell Transplantation
Volume19
Issue number8
DOIs
Publication statusPublished - 2010

Keywords

  • Engraftment
  • Human model
  • Islet transplantation
  • Mouse model
  • Portal vein

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

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