title: Basophil FcepsilonRI histamine release parallels expression of Src-homology 2-containing inositol phosphatases in chronic idiopathic urticaria.
abstract: BACKGROUND
  Basophils are implicated in the pathogenesis of chronic idiopathic urticaria (CIU). Autoantibodies to the IgE receptor (FcepsilonRI) and serum histamine releasing activity have been detected in some subjects with CIU, although their role in vivo is unclear. Basophils of patients with CIU have altered FcepsilonRI-mediated histamine release (HR); however, the mechanism is unknown. In the basophil FcepsilonRI signaling pathway, protein levels of Src-homology 2-containing-5'-inositol phosphatase (SHIP)-1 are inversely correlated with the release of mediators or releasability. A related phosphatase, SHIP-2, is a negative regulator of monocyte IgG receptor (FcgammaR) signaling . We hypothesized that SHIP levels are altered in CIU basophils.
  
  
  METHODS
  Blood basophils were isolated from cold urticaria, CIU, or normal donors, and FcepsilonRI-dependent and independent HR were quantified. Protein levels of SHIP-1, SHIP-2, spleen tyrosine kinase, and phosphorylated Akt were determined by Western blotting. Subjects' serum was tested for serum histamine releasing activity and anti-FcepsilonRIalpha antibodies.
  
  
  RESULTS
  CIU basophils displayed a bimodal response to anti-IgE activation. One half of CIU subjects' basophils had reductions in anti-IgE-induced HR and were designated nonresponders (CIU NR). CIU NR basophil HR remained diminished at 10-fold to 30-fold higher doses of anti-IgE. CIU anti-IgE responder basophils had HR similar to normal subjects. SHIP-1 and SHIP-2 proteins were increased in CIU NR basophils and were linked to reduced phosphoAkt after anti-IgE stimulation. CIU basophil anti-IgE response was not related to the presence of serologic factors.
  
  
  CONCLUSIONS
  In CIU basophils, the observed changes in FcepsilonRI signaling pathway molecule expression may underlie changes in releasability.
  
  
  CONCLUSIONS
  Patients with CIU can be segregated on the basis of basophil functional phenotype.
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Becky M
authors.initials: BM
authors.lastname: Vonakis
authors.forename: Kavitha
authors.initials: K
authors.lastname: Vasagar
authors.forename: Scott P
authors.initials: SP
authors.lastname: Gibbons
authors.forename: Laura
authors.initials: L
authors.lastname: Gober
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Sterba
authors.forename: Hyeyoun
authors.initials: H
authors.lastname: Chang
authors.forename: Sarbjit S
authors.initials: SS
authors.lastname: Saini
mesh_terms: D001491:Basophils / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood; D002908:Chronic Disease; D006636:Histamine Release; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D017455:Receptors, IgE / Q000502:physiology*; D015398:Signal Transduction; D000072377:Syk Kinase; D000090324:Tumor Protein, Translationally-Controlled 1; D014581:Urticaria / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D000090324:Tumor Protein, Translationally-Controlled 1; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases