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

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 1; pp. 55 - 65
• Main Authors: PIEMONTI, Lorenzo, LEONE, Biagio Eugenio, ALDRIGHETTI, Luca, SECCHI, Antonio, DI CARLO, Valerio, ALLAVENA, Paola, BERTUZZI, Federico, NANO, Rita, SACCANI, Alessandra, MONTI, Paolo, MAFFI, Paola, BIANCHI, Giancarlo, SICA, Antonio, PERI, Giuseppe, MELZI, Raffaella
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.2002
• Subjects: Adult; Biological and medical sciences; Blotting, Northern; Cells, Cultured; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Chemokine CCL2 - pharmacology; Chemokines; Chemotaxis, Leukocyte - drug effects; Cytokines; Cytokines - pharmacology; Diabetes; Diabetes Mellitus, Type 1 - surgery; Diabetic Nephropathies - surgery; Enzyme-Linked Immunosorbent Assay; Enzymes; Female; Gene Expression Regulation; Growth factors; Humans; Hybridization; Immunosuppression; Insulin; Insulin - metabolism; Insulin Secretion; Islands of Langerhans; Islets of Langerhans; Islets of Langerhans - metabolism; Islets of Langerhans Transplantation - physiology; Kidney Transplantation; Male; Middle Aged; Monocytes - physiology; Pancreatic beta cell transplantation; Pancreatic beta cells; Physiological aspects; Proteins; Transplantation; Transplants & implants; Tumor necrosis factor-TNF
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.1.55

Human Pancreatic Islets Produce and Secrete MCP-1/CCL2: Relevance in Human Islet Transplantation Lorenzo Piemonti 1 , Biagio Eugenio Leone 2 , Rita Nano 1 , Alessandra Saccani 3 , Paolo Monti 1 , Paola Maffi 4 , Giancarlo Bianchi 3 , Antonio Sica 3 , Giuseppe Peri 3 , Raffaella Melzi 1 , Luca Aldrighetti 1 , Antonio Secchi 4 , Valerio Di Carlo 1 , Paola Allavena 3 and Federico Bertuzzi 1 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 Abstract 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-1β, tumor necrosis factor-α) 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 β-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. Footnotes Address correspondence and reprint requests to Lorenzo Piemonti and Federico Bertuzzi, Laboratory of Experimental Surgery, S. Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan. E-mail: piemonti.lorenzo{at}hsr.it and bertuzzi.federico{at}hsr.it . Received for publication 5 April 2001 and accepted in revised form 28 September 2001. DAB, diaminobenzidine; ELISA, enzyme-linked immunosorbent assay; GAD, glutamic acid decarboxylase; IFN-γ, γ-interferon; IL, interleukin; ISH, in situ hybridization; LPS, lipopolysaccharide; MCP-1, monocyte chemoattractant protein-1; MIF, migration inhibitory factor; PDGF, platelet-derived growth factor; RPA, RNAse protection assay; TNF-α, tumor necrosis factor-α