PMID- 11756323 OWN - NLM STAT- MEDLINE DCOM- 20020213 LR - 20211203 IS - 0012-1797 (Print) IS - 0012-1797 (Linking) VI - 51 IP - 1 DP - 2002 Jan TI - Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation. PG - 55-65 AB - We investigated the capacity of human islets to produce monocyte chemoattractant protein-1 (MCP-1). Primary cultures of pancreatic islets expressed and secreted MCP-1, as determined by Northern blot, immunohistochemistry, in situ hybridization, and enzyme-linked immunosorbent assay. The produced MCP-1 was biologically active as it attracted monocytes in chemotaxis assay, and chemotactic activity was almost abrogated by a neutralizing anti-MCP-1 monoclonal antibody. Expression of MCP-1 was increased by primary inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha) and lipopolysaccharide at both the mRNA and protein levels but not by glucose. However, MCP-1 did not modulate insulin secretion. MCP-1 secreted by pancreatic islets plays a relevant role in the clinical outcome of islet transplant in patients with type 1 diabetes. In fact, low MCP-1 secretion resulted as the most relevant factor for long-lasting insulin independence. This finding opens new approaches in the management of human islet transplantation. Finally, the finding that MCP-1 appears constitutively present in normal human islet beta-cells (immunohistochemistry and in situ hybridization), in the absence of an inflammatory infiltrate, suggests that this chemokine could have functions other than monocyte recruitment and opens a new link between the endocrine and immune systems. FAU - Piemonti, Lorenzo AU - Piemonti L AD - Laboratory of Experimental Surgery, Surgical Department, S. Raffaele Scientific Institute, Via Olgettina, Milan, Italy. University of Milano Bicocca, Milan, Italy. piemonti.lorenzo@hsr.it FAU - Leone, Biagio Eugenio AU - Leone BE FAU - Nano, Rita AU - Nano R FAU - Saccani, Alessandra AU - Saccani A FAU - Monti, Paolo AU - Monti P FAU - Maffi, Paola AU - Maffi P FAU - Bianchi, Giancarlo AU - Bianchi G FAU - Sica, Antonio AU - Sica A FAU - Peri, Giuseppe AU - Peri G FAU - Melzi, Raffaella AU - Melzi R FAU - Aldrighetti, Luca AU - Aldrighetti L FAU - Secchi, Antonio AU - Secchi A FAU - Di Carlo, Valerio AU - Di Carlo V FAU - Allavena, Paola AU - Allavena P FAU - Bertuzzi, Federico AU - Bertuzzi F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (Insulin) SB - IM MH - Adult MH - Blotting, Northern MH - Cells, Cultured MH - Chemokine CCL2/*genetics/metabolism/pharmacology MH - Chemotaxis, Leukocyte/drug effects MH - Cytokines/pharmacology MH - Diabetes Mellitus, Type 1/*surgery MH - Diabetic Nephropathies/surgery MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Gene Expression Regulation MH - Humans MH - Immunosuppression Therapy MH - Insulin/*metabolism MH - Insulin Secretion MH - Islets of Langerhans/*metabolism MH - *Islets of Langerhans Transplantation/*physiology MH - Kidney Transplantation MH - Male MH - Middle Aged MH - Monocytes/physiology EDAT- 2002/01/05 10:00 MHDA- 2002/02/14 10:01 CRDT- 2002/01/05 10:00 PHST- 2002/01/05 10:00 [pubmed] PHST- 2002/02/14 10:01 [medline] PHST- 2002/01/05 10:00 [entrez] AID - 10.2337/diabetes.51.1.55 [doi] PST - ppublish SO - Diabetes. 2002 Jan;51(1):55-65. doi: 10.2337/diabetes.51.1.55.