Shwachman-Diamond syndrome neutrophils have altered chemoattractant-induced F-actin polymerization and polarization characteristics.

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.

• Authors: Claudia Orelio, Taco W Kuijpers
• Journal: Haematologica (Haematologica) Vol. 94 Issue 3 Pg. 409-13 (Mar 2009) ISSN: 1592-8721 [Electronic] Italy
• PMID: 19211642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Chemotactic Factors
• Polymers
• Proteins
• SBDS protein, human
• Green Fluorescent Proteins
• N-Formylmethionine Leucyl-Phenylalanine
• Complement C5a
• rac2 GTP-binding protein
• rac GTP-Binding Proteins

Topics

• Abnormalities, Multiple (blood, genetics, pathology)
• Actins (metabolism)
• Adolescent
• Adult
• Animals
• Cell Line, Tumor
• Cell Polarity
• Cells, Cultured
• Chemotactic Factors (pharmacology)
• Child
• Child, Preschool
• Complement C5a (pharmacology)
• Exocrine Pancreatic Insufficiency (pathology)
• Fluorescent Antibody Technique
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Mutation
• N-Formylmethionine Leucyl-Phenylalanine (pharmacology)
• Neutrophils (drug effects, metabolism, pathology)
• Polymers
• Proteins (genetics, metabolism)
• Syndrome
• Transfection
• Young Adult
• rac GTP-Binding Proteins (genetics, metabolism)