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Diabetes 51:55-65, 2002
© 2002 by the American Diabetes Association, Inc.

Human Pancreatic Islets Produce and Secrete MCP-1/CCL2: Relevance in Human Islet Transplantation

Lorenzo Piemonti1, Biagio Eugenio Leone2, Rita Nano1, Alessandra Saccani3, Paolo Monti1, Paola Maffi4, Giancarlo Bianchi3, Antonio Sica3, Giuseppe Peri3, Raffaella Melzi1, Luca Aldrighetti1, Antonio Secchi4, Valerio Di Carlo1, Paola Allavena3, and Federico Bertuzzi1

1 Laboratory of Experimental Surgery, Surgical Department, S. Raffaele Scientific Institute, Via Olgettina, Milan, Italy
2 University of Milano Bicocca, Milan, Italy
3 Department of Immunology and Cell Biology, "Mario Negri" Institute, Via Eritrea, Milan, Italy
4 Medicine Department, S. Raffaele Scientific Institute, Via Olgettina, Milan, Italy

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-1ß, 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 ß-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.


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