Immunocytochemical detection and characterization of intrahepatic human pancreatic islets after combined liver-islet allotransplantation.
The unique availability of an explanted liver-islet allograft, removed for primary nonfunction of the liver, led us to evaluate distribution and phenotype of exocrine and endocrine components of the pancreatic graft. Immunocytochemistry was used to map patterns of gene products for islet hormones, proprotein processing enzymes, panneuroendocrine markers, and pancreatic exocrine markers. When compared with age-matched control pancreases, insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-producing cells were similarly represented and distributed within the grafted islet. We also demonstrate that the intrahepatic transplanted islets retained the enzyme machinery able to process the hormone precursors into bioactive fragments. In the clinical setting, this resulted in an immediate functioning of the graft and insulin-independence of the patient one month after transplantation. The purity in islets, as assessed by immunocytochemistry with antibodies to tissue constituents of endocrine and exocrine lineages, was around 40%. Despite the massive intraportal presence of pancreatic acinar tissue, no signs or symptoms attributable to ectopic hypersecretion of exocrine enzymes occurred. In fact, when tested with antibodies to such enzymes, low levels of immunoreactivity were observed in the grafted acinar cells.
Scopsi
L
L
Department of Pathology, Istituto Nazionale Tumori, Milan, Italy.
Andreola
S
S
Socci
C
C
Bertuzzi
F
F
Di Carlo
V
V
Pozza
G
G
Rilke
F
F
Gennari
L
L
Colella
G
G
Regalia
E
E
D015415:Biomarkers / Q000032:analysis; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000032:analysis; D018278:Carcinoma, Neuroendocrine / Q000556:secondary / Q000601:surgery; D005934:Glucagon / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007328:Insulin / Q000032:analysis; D016381:Islets of Langerhans Transplantation / Q000473:pathology* / Q000502:physiology; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery; D016031:Liver Transplantation / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000032:analysis; D009097:Multienzyme Complexes; D010190:Pancreatic Neoplasms / Q000601:surgery; D010191:Pancreatic Polypeptide / Q000032:analysis; D011384:Proinsulin / Q000032:analysis; D012086:Reoperation; D013004:Somatostatin / Q000032:analysis; D013381:Subtilisins / Q000032:analysis; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D015415:Biomarkers; D007328:Insulin; D009097:Multienzyme Complexes; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D011384:Proinsulin; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D002268:Carboxypeptidases; D043423:Carboxypeptidase H; D013381:Subtilisins