TY - JOUR
T1 - Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome
AU - Necchi, Vittorio
AU - Minelli, Antonella
AU - Sommi, Patrizia
AU - Vitali, Agostina
AU - Caruso, Roberta
AU - Longoni, Daniela
AU - Frau, Maria Rita
AU - Nasi, Cristina
AU - De Gregorio, Fabiola
AU - Zecca, Marco
AU - Ricci, Vittorio
AU - Danesino, Cesare
AU - Solcia, Enrico
PY - 2012/7/1
Y1 - 2012/7/1
N2 - Background Shwachman-Diamond syndrome is an autosomal recessive disorder in which severe bone marrow dysfunction causes neutropenia and an increased risk of leukemia. Recently, novel particulate cytoplasmic structures, rich in ubiquitinated and proteasomal proteins, have been detected in epithelial cells and neutrophils from patients with Helicobacter pylori gastritis and several epithelial neoplasms. Design and Methods Blood neutrophils from 13 cases of Shwachman-Diamond syndrome - ten with and three without SBDS gene mutation - and ten controls were investigated by confocal microscopy and ultrastructural immunocytochemistry using antibodies against ubiquitinated proteins, proteasomes, p62 protein, and Helicobacter pylori VacA, urease and outer membrane proteins. Results Many extensively disseminated particulate cytoplasmic structures, accounting for 22.78±5.57% (mean ± standard deviation) of the total cytoplasm, were found in blood neutrophils from mutated Shwachman-Diamond syndrome patients. The particulate cytoplasmic structures showed immunoreactivity for polyubiquitinated proteins and proteasomes, but no reactivity for Helicobacter pylori products, which are present in particulate cytoplasmic structures of Helicobacter pylori-positive gastritis. Neutrophils from patients with Shwachman-Diamond syndrome frequently showed p62-positive autophagic vacuoles and apoptotic changes in 5% of cells. No particulate cytoplasmic structures were observed in most control neutrophils; however, in a few cells from two cases we noted focal development of minute particulate cytoplasmic structures, accounting for 0.74±0.56% of the total cytoplasm (P
AB - Background Shwachman-Diamond syndrome is an autosomal recessive disorder in which severe bone marrow dysfunction causes neutropenia and an increased risk of leukemia. Recently, novel particulate cytoplasmic structures, rich in ubiquitinated and proteasomal proteins, have been detected in epithelial cells and neutrophils from patients with Helicobacter pylori gastritis and several epithelial neoplasms. Design and Methods Blood neutrophils from 13 cases of Shwachman-Diamond syndrome - ten with and three without SBDS gene mutation - and ten controls were investigated by confocal microscopy and ultrastructural immunocytochemistry using antibodies against ubiquitinated proteins, proteasomes, p62 protein, and Helicobacter pylori VacA, urease and outer membrane proteins. Results Many extensively disseminated particulate cytoplasmic structures, accounting for 22.78±5.57% (mean ± standard deviation) of the total cytoplasm, were found in blood neutrophils from mutated Shwachman-Diamond syndrome patients. The particulate cytoplasmic structures showed immunoreactivity for polyubiquitinated proteins and proteasomes, but no reactivity for Helicobacter pylori products, which are present in particulate cytoplasmic structures of Helicobacter pylori-positive gastritis. Neutrophils from patients with Shwachman-Diamond syndrome frequently showed p62-positive autophagic vacuoles and apoptotic changes in 5% of cells. No particulate cytoplasmic structures were observed in most control neutrophils; however, in a few cells from two cases we noted focal development of minute particulate cytoplasmic structures, accounting for 0.74±0.56% of the total cytoplasm (P
KW - Apoptosis
KW - Autophagy
KW - Particulate cytoplasmic structure
KW - Proteasome
KW - Shwachman-Diamond syndrome
KW - Ubiquitin
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U2 - 10.3324/haematol.2011.048462
DO - 10.3324/haematol.2011.048462
M3 - Article
C2 - 22271888
AN - SCOPUS:84863889048
VL - 97
SP - 1057
EP - 1063
JO - Haematologica
JF - Haematologica
SN - 0390-6078
IS - 7
ER -