title: Restoration of podosomes and chemotaxis in Wiskott-Aldrich syndrome macrophages following induced expression of WASp.
abstract: We used a direct-viewing (Dunn) chemotaxis chamber to analyse the chemotactic responses of human normal and Wiskott-Aldrich syndrome (WAS) macrophages to the cytokine colony stimulating factor-1 (CSF-1). In five patients with classic WAS, where specialised adhesion complexes called podosomes are absent, chemotaxis of macrophages was abolished. The deficient chemotactic responses of WAS macrophages following cytokine stimulation could be correlated with abnormalities in cell polarisation and actin organisation. In a series of cell microinjection studies we found that normal chemotactic responses were restored in WASp macrophages transfected with a full-length human WAS construct. Expression of exogenous WAS protein (WASp) in these cells also restored normal polarised cell morphology and the ability to form podosomes.
authors.affiliation: The Randall Centre, King's College London, London SE1 1UL, UK. gareth.jones@kcl.ac.uk
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Jones
authors.forename: Daniel
authors.initials: D
authors.lastname: Zicha
authors.forename: Graham A
authors.initials: GA
authors.lastname: Dunn
authors.forename: Mike
authors.initials: M
authors.lastname: Blundell
authors.forename: Adrian
authors.initials: A
authors.lastname: Thrasher
mesh_terms: D000199:Actins / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D011554:Pseudopodia / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: D000199:Actins; D011506:Proteins; D011994:Recombinant Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D016173:Macrophage Colony-Stimulating Factor