Document Detail

Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome.
MedLine Citation:
PMID:  22271888     Owner:  NLM     Status:  MEDLINE    
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<0.001 versus particulate cytoplasmic structures from mutated Shwachman-Diamond syndrome patients). Neutrophils from non-mutated Shwachman-Diamond-syndrome-like patients resembled controls in two cases, and a third case showed particulate cytoplasmic structure patterns intermediate between those in controls and those in mutated Shwachman-Diamond syndrome patients.
CONCLUSIONS: Particulate cytoplasmic structures are a prominent feature of neutrophils from patients with Shwachman-Diamond syndrome. They may help us to understand the mechanism of granulocyte dysfunction and the neoplastic risk of the disease.
Vittorio Necchi; Antonella Minelli; Patrizia Sommi; Agostina Vitali; Roberta Caruso; Daniela Longoni; Maria Rita Frau; Cristina Nasi; Fabiola De Gregorio; Marco Zecca; Vittorio Ricci; Cesare Danesino; Enrico Solcia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-22
Journal Detail:
Title:  Haematologica     Volume:  97     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-16     Completed Date:  2012-12-31     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  1057-63     Citation Subset:  IM    
Department of Human Pathology and Genetics, University of Pavia and Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
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MeSH Terms
Bacterial Proteins / genetics,  metabolism
Bone Marrow / metabolism,  pathology*
Bone Marrow Diseases / complications,  genetics,  pathology*
Child, Preschool
Cytoplasmic Structures / genetics,  metabolism*,  ultrastructure
Exocrine Pancreatic Insufficiency / complications,  genetics,  pathology*
Gene Expression
Lipomatosis / complications,  genetics,  pathology*
Microscopy, Confocal
Neutropenia / complications,  genetics,  pathology*
Neutrophils / metabolism*,  ultrastructure
Proteasome Endopeptidase Complex / genetics,  metabolism*,  ultrastructure
Proteins / genetics,  metabolism
RNA-Binding Proteins / genetics,  metabolism
Ubiquitin / metabolism
Ubiquitinated Proteins / genetics,  metabolism
Reg. No./Substance:
0/Bacterial Proteins; 0/P62 protein, human; 0/Proteins; 0/RNA-Binding Proteins; 0/SBDS protein, human; 0/Ubiquitin; 0/Ubiquitinated Proteins; 0/VacA protein, Helicobacter pylori; EC Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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