title: Aspirin augments IgE-mediated histamine release from human peripheral basophils via Syk kinase activation.
abstract: BACKGROUND
  Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise-induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release.
  
  
  METHODS
  The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated.
  
  
  RESULTS
  Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucyl-phenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls.
  
  
  CONCLUSIONS
  Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.
authors.affiliation: Department of Pathophysiology and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsuo
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yokooji
authors.forename: Hironobu
authors.initials: H
authors.lastname: Morita
authors.forename: Mina
authors.initials: M
authors.lastname: Ooi
authors.forename: Kana
authors.initials: K
authors.lastname: Urata
authors.forename: Kaori
authors.initials: K
authors.lastname: Ishii
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Takahagi
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Yanase
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hiragun
authors.forename: Shoji
authors.initials: S
authors.lastname: Mihara
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hide
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001250:Asthma, Exercise-Induced / Q000276:immunology; D001491:Basophils / Q000187:drug effects* / Q000276:immunology; D001565:Benzoates / Q000494:pharmacology; D000001:Calcimycin / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002908:Chronic Disease; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005512:Food Hypersensitivity / Q000150:complications / Q000276:immunology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D013645:Tartrazine / Q000494:pharmacology; D014581:Urticaria / Q000276:immunology; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001565:Benzoates; D016861:Cyclooxygenase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D007073:Immunoglobulin E; D000001:Calcimycin; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D013645:Tartrazine; D001241:Aspirin