Restoration of podosomes and chemotaxis in Wiskott-Aldrich syndrome macrophages following induced expression of WASp.
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.
Jones
Gareth E
GE
The Randall Centre, King's College London, London SE1 1UL, UK. gareth.jones@kcl.ac.uk
Zicha
Daniel
D
Dunn
Graham A
GA
Blundell
Mike
M
Thrasher
Adrian
A
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
D000199:Actins; D011506:Proteins; D011994:Recombinant Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D016173:Macrophage Colony-Stimulating Factor