title: 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.affiliation: Sanquin Research and Landsteiner Laboratory Dept. Blood Cell Research Phagocyte Laboratory, The Netherlands.
authors.forename: Claudia
authors.initials: C
authors.lastname: Orelio
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000015:Abnormalities, Multiple / Q000097:blood* / Q000235:genetics / Q000473:pathology; D000199:Actins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D016764:Cell Polarity; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D015936:Complement C5a / Q000494:pharmacology; D010188:Exocrine Pancreatic Insufficiency / Q000473:pathology; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011108:Polymers; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013577:Syndrome; D014162:Transfection; D055815:Young Adult; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000097766:RAC2 GTP-Binding Protein
chemical_list: D000199:Actins; D002630:Chemotactic Factors; D015936:Complement C5a; D049452:Green Fluorescent Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011108:Polymers; D011506:Proteins; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C470521:SBDS protein, human