Impaired Integrin-Dependent Function in Wiskott-Aldrich Syndrome Protein-Deficient Murine and Human Neutrophils

Hong Zhang, Ulrich Y. Schaff, Chad E. Green, Hua Chen, Melissa R. Sarantos, Yongmei Hu, Diane Wara, Scott I. Simon, Clifford A. Lowell

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency that manifests as increased susceptibility to many pathogens. Although the spectrum of infections suffered by WAS patients is consistent with defects in neutrophil (PMN) function, the consequences of WAS protein (WASp) deficiency on this innate immune cell have been unclear. We report that deficiency of WASp in both human and murine PMNs resulted in profound defects in clustering of β2 integrins, leading to defective adhesion and transendothelial migration under conditions of physiologic shear flow. Wild-type PMNs redistributed clustered β2 integrins to the uropod of the cell during active migration, whereas WASp-deficient cells remain unpolarized. The WASp-deficient PMNs also showed reduced integrin-dependent activation of degranulation and respiratory burst. PMNs from a WAS patient manifested similar defects in integrin clustering and signaling. These results suggest that impaired β2 integrin function in WASp-deficient PMNs may contribute substantially to the clinical immunodeficiency suffered by WAS patients.

Original languageEnglish (US)
Pages (from-to)285-295
Number of pages11
Issue number2
StatePublished - Aug 2006



ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology


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