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Stromal-derived factor-1 abolishes constitutive apoptosis of WHIM syndrome neutrophils harbouring a truncating CXCR4
Duangmanee Sanmun1, Daniel Garwicz, C I Edvard Smith
1Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Abstract:
Warts, hypogammaglobulinaemia, infections, myelokathexis (WHIM) syndrome is an inherited immune disorder associated with CXCR4 gene mutations. Recent studies suggested that impaired receptor downregulation and enhanced chemotactic responsiveness to stromal-derived factor-1 (SDF-1), the sole cognate ligand for CXCR4, may account for the characteristic features of WHIM patients. This study evaluated whether the interaction of SDF-1 with CXCR4 could block constitutive apoptosis of peripheral blood neutrophils from congenital neutropenia patients and controls. SDF-1 was found to be a potent anti-apoptotic factor for WHIM neutrophils harbouring a truncating CXCR4 mutation, but not for neutrophils from control individuals, thus supporting the notion that such mutations may confer enhanced functional responses.
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