Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation.
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.
Piemonti
Lorenzo
L
Laboratory of Experimental Surgery, Surgical Department, S. Raffaele Scientific Institute, Via Olgettina, Milan, Italy. University of Milano Bicocca, Milan, Italy. piemonti.lorenzo@hsr.it
Leone
Biagio Eugenio
BE
Nano
Rita
R
Saccani
Alessandra
A
Monti
Paolo
P
Maffi
Paola
P
Bianchi
Giancarlo
G
Sica
Antonio
A
Peri
Giuseppe
G
Melzi
Raffaella
R
Aldrighetti
Luca
L
Secchi
Antonio
A
Di Carlo
Valerio
V
Allavena
Paola
P
Bertuzzi
Federico
F
D000328:Adult; D015152:Blotting, Northern; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007165:Immunosuppression Therapy; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology
D018932:Chemokine CCL2; D016207:Cytokines; D007328:Insulin