PMID- 15110609 OWN - NLM STAT- MEDLINE DCOM- 20041116 LR - 20181130 IS - 0041-1345 (Print) IS - 0041-1345 (Linking) VI - 36 IP - 3 DP - 2004 Apr TI - In vitro modulation of monocyte chemoattractant protein-1 release in human pancreatic islets. PG - 607-8 AB - Islet transplantation is a new approach to treat type 1 diabetic patients. Despite its great potential and progressively increasing success rate, islet engraftment still represents an unsolved problem. Only part of the transplanted beta-cell mass survives after infusion due to hypoxia and inflammatory reactions, principally mediated by macrophages. We have demonstrated that human islets release monocyte chemoattractant protein-1 (MCP-1), one of the most powerful macrophage chemokines, which may impair the fate of a transplant. In this study we have attempted to modulate in vitro MCP-1 release by human islets. Human islets isolated using the automated method were cultured in CMRL or M199 standard culture media alone or supplemented with (1) two intracellular kinase inhibitors (10 micromol/L RO8220, a protein kinase C inhibitor, and rcAMP 20 micromol/L, a protein kinase A inhibitor) or (2) two antioxidant and cell-protective agents (vitamin E, vitamin B); or (3) immunosuppressive drugs (0.001 to 10 ng/mL cyclosporine, 0.1 to 100 ng/mL rapamycin, 0.1 to 10 ng/mL tacrolimus, 0.001 to 10 ng/mL mycophenolate acid). We observed that the only culture condition that significantly decreased MCP-1 in human islets were CMRL (31 +/- 12 in CMRL vs 539 +/- 184 pg/mL, in M199, P <.05) or cyclosporine (514 +/- 83 pg/mL in control islet vs 307 +/- 13, 231 +/- 44, 192 +/- 4, 242 +/- 113, 169 +/- 15 pg/mL in islet plus cyclosporine ranging from 0.001 to 10 ng/mL, respectively, P >.05). The capacity of in vitro factors to decrease human islet MCP-1 release suggests strategies to increase the success of islet transplantation. FAU - Marzorati, S AU - Marzorati S AD - Surgical Department, San Raffaele Scientific Institute, Milan, Italy. FAU - Melzi, R AU - Melzi R FAU - Nano, R AU - Nano R FAU - Antonioli, B AU - Antonioli B FAU - Di Carlo, V AU - Di Carlo V FAU - Piemonti, L AU - Piemonti L FAU - Bertuzzi, F AU - Bertuzzi F LA - eng PT - Journal Article PL - United States TA - Transplant Proc JT - Transplantation proceedings JID - 0243532 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Culture Media) RN - 0 (Cytokines) SB - IM MH - Cell Culture Techniques/methods MH - Cell Separation/methods MH - Chemokine CCL2/*metabolism MH - Culture Media MH - Cytokines/metabolism MH - Diabetes Mellitus, Type 1/surgery MH - Humans MH - Inflammation/prevention & control MH - Islets of Langerhans/cytology/*metabolism MH - Islets of Langerhans Transplantation MH - Macrophages/cytology MH - Monocytes/cytology EDAT- 2004/04/28 05:00 MHDA- 2004/11/17 09:00 CRDT- 2004/04/28 05:00 PHST- 2004/04/28 05:00 [pubmed] PHST- 2004/11/17 09:00 [medline] PHST- 2004/04/28 05:00 [entrez] AID - S0041134504001927 [pii] AID - 10.1016/j.transproceed.2004.02.048 [doi] PST - ppublish SO - Transplant Proc. 2004 Apr;36(3):607-8. doi: 10.1016/j.transproceed.2004.02.048.