[HTML][HTML] Shwachman-Diamond syndrome neutrophils have altered chemoattractant-induced F-actin polymerization and polarization characteristics

C Orelio, TW Kuijpers - haematologica, 2009 - ncbi.nlm.nih.gov
C Orelio, TW Kuijpers
haematologica, 2009ncbi.nlm.nih.gov
Shwachman-Diamond syndrome is a hereditary disorder characterized by pancreatic
insufficiency and bone marrow failure. Most Shwachman-Diamond syndrome patients have
mutations in the SBDS gene located at chromosome 7 and suffer from recurrent infections,
due to neutropenia in combination with impaired neutrophil chemotaxis. Currently, the role
of the actin cytoskeleton in Shwachman-Diamond syndrome neutrophils has not been
investigated. Therefore, we performed immunofluorescence for SBDS and F-actin on human …
Abstract
Shwachman-Diamond syndrome is a hereditary disorder characterized by pancreatic insufficiency and bone marrow failure. Most Shwachman-Diamond syndrome patients have mutations in the SBDS gene located at chromosome 7 and suffer from recurrent infections, due to neutropenia in combination with impaired neutrophil chemotaxis. Currently, the role of the actin cytoskeleton in Shwachman-Diamond syndrome neutrophils has not been investigated. Therefore, we performed immunofluorescence for SBDS and F-actin on human neutrophilic cells. Additionally, we examined in control neutrophils and cells from genetically defined Shwachman-Diamond syndrome patients F-actin polymerization and cytoskeletal polarization characteristics upon chemoattractant stimulation. These studies showed that SBDS and F-actin co-localize in neutrophilic cells and that F-actin polymerization and depolymerization characteristics are altered in Shwachman-Diamond syndrome neutrophils as compared to control neutrophils in response to both fMLP and C5a. Moreover, F-actin cytoskeletal polarization is delayed in Shwachman-Diamond syndrome neutrophils. Thus, Shwachman-Diamond syndrome neutrophils have aberrant chemoattractant-induced F-actin properties which might contribute to the impaired neutrophil chemotaxis.
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