Human pancreatic islets produce and secrete MCP-1/CCL2

Relevance in human islet transplantation

Lorenzo Piemonti, Biagio Eugenio Leone, Rita Nano, Alessandra Saccani, Paolo Monti, Paola Maffi, Giancarlo Bianchi, Antonio Sica, Giuseppe Peri, Raffaella Melzi, Luca Aldrighetti, Antonio Secchi, Valerio Di Carlo, Paola Allavena, Federico Bertuzzi

Research output: Contribution to journalArticle

215 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)55-65
Number of pages11
JournalDiabetes
Volume51
Issue number1
Publication statusPublished - 2002

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Islets of Langerhans Transplantation
Chemokine CCL2
Islets of Langerhans
In Situ Hybridization
Monocytes
Immunohistochemistry
Insulin
Endocrine System
Chemotaxis
Type 1 Diabetes Mellitus
Interleukin-1
Chemokines
Northern Blotting
Lipopolysaccharides
Immune System
Tumor Necrosis Factor-alpha
Enzyme-Linked Immunosorbent Assay
Monoclonal Antibodies
Cytokines
Transplants

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Human pancreatic islets produce and secrete MCP-1/CCL2 : Relevance in human islet transplantation. / Piemonti, Lorenzo; Leone, Biagio Eugenio; Nano, Rita; Saccani, Alessandra; Monti, Paolo; Maffi, Paola; Bianchi, Giancarlo; Sica, Antonio; Peri, Giuseppe; Melzi, Raffaella; Aldrighetti, Luca; Secchi, Antonio; Di Carlo, Valerio; Allavena, Paola; Bertuzzi, Federico.

In: Diabetes, Vol. 51, No. 1, 2002, p. 55-65.

Research output: Contribution to journalArticle

Piemonti, L, Leone, BE, Nano, R, Saccani, A, Monti, P, Maffi, P, Bianchi, G, Sica, A, Peri, G, Melzi, R, Aldrighetti, L, Secchi, A, Di Carlo, V, Allavena, P & Bertuzzi, F 2002, 'Human pancreatic islets produce and secrete MCP-1/CCL2: Relevance in human islet transplantation', Diabetes, vol. 51, no. 1, pp. 55-65.
Piemonti, Lorenzo ; Leone, Biagio Eugenio ; Nano, Rita ; Saccani, Alessandra ; Monti, Paolo ; Maffi, Paola ; Bianchi, Giancarlo ; Sica, Antonio ; Peri, Giuseppe ; Melzi, Raffaella ; Aldrighetti, Luca ; Secchi, Antonio ; Di Carlo, Valerio ; Allavena, Paola ; Bertuzzi, Federico. / Human pancreatic islets produce and secrete MCP-1/CCL2 : Relevance in human islet transplantation. In: Diabetes. 2002 ; Vol. 51, No. 1. pp. 55-65.
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T2 - Relevance in human islet transplantation

AU - Piemonti, Lorenzo

AU - Leone, Biagio Eugenio

AU - Nano, Rita

AU - Saccani, Alessandra

AU - Monti, Paolo

AU - Maffi, Paola

AU - Bianchi, Giancarlo

AU - Sica, Antonio

AU - Peri, Giuseppe

AU - Melzi, Raffaella

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AU - Secchi, Antonio

AU - Di Carlo, Valerio

AU - Allavena, Paola

AU - Bertuzzi, Federico

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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-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.

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