The Polarization Defect of Wiskott-Aldrich Syndrome Macrophages Is Linked to Dislocalization of the Arp2/3 Complex

• DOI: 10.4049/jimmunol.165.1.221
• Publication Date: 2014-04-21T00:07:57Z
• Authors: Stefan Linder; Henry Higgs; Katharina Hüfner; Klaus Schwarz; Ulrich Pannicke; Martin Aepfelbacher
• Keywords: Podosome; Wiskott–Aldrich syndrome protein; Wiskott–Aldrich syndrome

Abstract Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder originally characterized by the clinical triad eczema, thrombocytopenia, and severe immunodeficieny, with recurrent bacterial viral infections, indicating a profound immune cell defect. Such altered cells include monocytes, macrophages, dendritic cells, which were reported to display disturbed polarization or chemotaxis. WAS caused mutations in protein (WASp), thought organize actin cytoskeleton through Arp2/3 complex. Here we show that complex integral part of podosomes, actin-rich adhesion structures macrophages fail into podosomes. We also demonstrate microinjection C-terminal acidic stretch WASp normal displaces from podosomes and, combination chemoattractant stimulation induces phenotype resembling polarization-defective stimulated macrophages. These findings point important role migration cells.