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

Haematologica. 2009 Mar;94(3):409-13. doi: 10.3324/haematol.13733. Epub 2009 Feb 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / blood*
  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / 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
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mutation
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Neutrophils / pathology
  • Polymers
  • Proteins / genetics
  • Proteins / metabolism*
  • RAC2 GTP-Binding Protein
  • Syndrome
  • Transfection
  • Young Adult
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism

Substances

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