Mast cells infiltrate pancreatic islets in human type 1 diabetes.
OBJECTIVE
Beta cell destruction in human type 1 diabetes occurs through the interplay of genetic and environmental factors, and is mediated by immune cell infiltration of pancreatic islets. In this study, we explored the role of mast cells as an additional agent in the pathogenesis of type 1 diabetes insulitis.


METHODS
Pancreatic tissue from donors without diabetes and with type 1 and 2 diabetes was studied using different microscopy techniques to identify islet-infiltrating cells. The direct effects of histamine exposure on isolated human islets and INS-1E cells were assessed using cell-survival studies and molecular mechanisms.


RESULTS
A larger number of mast cells were found to infiltrate pancreatic islets in samples from donors with type 1 diabetes, compared with those from donors without diabetes or with type 2 diabetes. Evidence of mast cell degranulation was observed, and the extent of the infiltration correlated with beta cell damage. Histamine, an amine that is found at high levels in mast cells, directly contributed to beta cell death in isolated human islets and INS-1E cells via a caspase-independent pathway.


CONCLUSIONS
These findings suggest that mast cells might be responsible, at least in part, for immune-mediated beta cell alterations in human type 1 diabetes. If this is the case, inhibition of mast cell activation and degranulation might act to protect beta cells in individuals with type 1 diabetes.
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Luisa
L
Martino
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Matilde
M
Masini
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Marco
M
Bugliani
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Lorella
L
Marselli
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Mara
M
Suleiman
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Ugo
U
Boggi
ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Tatiane C
TC
Nogueira
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Franco
F
Filipponi
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Margherita
M
Occhipinti
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Daniela
D
Campani
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Francesco
F
Dotta
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Farooq
F
Syed
ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Decio L
DL
Eizirik
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Piero
P
Marchetti
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126, Pisa, Italy. vincenzo.detata@med.unipi.it.
Vincenzo
V
De Tata
D000328:Adult; D000368:Aged; D002470:Cell Survival; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000473:pathology*; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology*; D055815:Young Adult
Histamine; Human islets; Insulitis; Mast cells; Type 1 diabetes; Type 2 diabetes