CHEMOTAXIS OF MACROPHAGES IS ABOLISHED IN THE WISKOTT-ALDRICH-SYNDROME

Wiskott-Aldrich syndrome (WAS) is a rare disease characterized by micr othrombocytopenia, eczema and immune deficiency. In this study a direc t-viewing chemotaxis chamber was used to analyse chemotactic responses of WAS neutrophils and macrophages in stable linear concentration gra dients. In five patients with classic WAS, chemotaxis of macrophages b ut not of neutrophils was found to be abolished, whereas the speed of random motility of both cell types was found to be indistinguishable f rom control cells. This supports the existence of an essential functio nal link, previously suggested by biochemical studies, between Cdc42, WAS protein (WASp) and the actin cytoskeleton in primary human macroph ages. Moreover, these data suggest that Cdc42-WASp-mediated filopodial extension is a requirement for chemotaxis but not for chemokinesis in these cells. Abnormal directional cell motility of macrophages and re lated antigen-presenting cells may play a significant part in the immu ne deficiency and eczema of WAS.