Role of CCL2/MCP-1 in Islet Transplantation
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2010-08-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368910X514639 |
| _version_ | 1828807769733464064 |
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| author | Raffaella Melzi Alessia Mercalli Valeria Sordi Elisa Cantarelli Rita Nano Paola Maffi Giovanni Sitia Luca G. Guidotti Antonio Secchi Ezio Bonifacio Lorenzo Piemonti |
| author_facet | Raffaella Melzi Alessia Mercalli Valeria Sordi Elisa Cantarelli Rita Nano Paola Maffi Giovanni Sitia Luca G. Guidotti Antonio Secchi Ezio Bonifacio Lorenzo Piemonti |
| author_sort | Raffaella Melzi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T08:30:38Z |
| format | Article |
| id | doaj.art-af365a0cb2974e7ebcc216191d657a9e |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-12T08:30:38Z |
| publishDate | 2010-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-af365a0cb2974e7ebcc216191d657a9e2022-12-22T00:31:07ZengSAGE PublishingCell Transplantation0963-68971555-38922010-08-011910.3727/096368910X514639Role of CCL2/MCP-1 in Islet TransplantationRaffaella Melzi0Alessia Mercalli1Valeria Sordi2Elisa Cantarelli3Rita Nano4Paola Maffi5Giovanni Sitia6Luca G. Guidotti7Antonio Secchi8Ezio Bonifacio9Lorenzo Piemonti10Beta Cell Biology Unit, Diabetes Research Institute, San Raffaele Scientific Institute, Milan, ItalyTransplant Unit, Department of Medicine, San Raffaele Scientific Institute, Milan, ItalyBeta Cell Biology Unit, Diabetes Research Institute, San Raffaele Scientific Institute, Milan, ItalyBeta Cell Biology Unit, Diabetes Research Institute, San Raffaele Scientific Institute, Milan, ItalyBeta Cell Biology Unit, Diabetes Research Institute, San Raffaele Scientific Institute, Milan, ItalyTransplant Unit, Department of Medicine, San Raffaele Scientific Institute, Milan, ItalyVirology & Immunopathology Unit, Diabetes Research Institute, San Raffaele Scientific Institute, Milan, ItalyVirology & Immunopathology Unit, Diabetes Research Institute, San Raffaele Scientific Institute, Milan, ItalyTransplant Unit, Department of Medicine, San Raffaele Scientific Institute, Milan, ItalyCenter for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, GermanyBeta Cell Biology Unit, Diabetes Research Institute, San Raffaele Scientific Institute, Milan, ItalyHigh 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.https://doi.org/10.3727/096368910X514639 |
| spellingShingle | Raffaella Melzi Alessia Mercalli Valeria Sordi Elisa Cantarelli Rita Nano Paola Maffi Giovanni Sitia Luca G. Guidotti Antonio Secchi Ezio Bonifacio Lorenzo Piemonti Role of CCL2/MCP-1 in Islet Transplantation Cell Transplantation |
| title | Role of CCL2/MCP-1 in Islet Transplantation |
| title_full | Role of CCL2/MCP-1 in Islet Transplantation |
| title_fullStr | Role of CCL2/MCP-1 in Islet Transplantation |
| title_full_unstemmed | Role of CCL2/MCP-1 in Islet Transplantation |
| title_short | Role of CCL2/MCP-1 in Islet Transplantation |
| title_sort | role of ccl2 mcp 1 in islet transplantation |
| url | https://doi.org/10.3727/096368910X514639 |
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