title: Stromal-derived factor-1 abolishes constitutive apoptosis of WHIM syndrome neutrophils harbouring a truncating CXCR4 mutation.
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.
authors.affiliation: Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Duangmanee
authors.initials: D
authors.lastname: Sanmun
authors.forename: Daniel
authors.initials: D
authors.lastname: Garwicz
authors.forename: C I Edvard
authors.initials: CI
authors.lastname: Smith
authors.forename: Jan
authors.initials: J
authors.lastname: Palmblad
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000473:pathology; D007239:Infections / Q000276:immunology / Q000473:pathology; D009154:Mutation; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome; D014860:Warts / Q000276:immunology* / Q000473:pathology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4