title: PGE suppresses excessive anti-IgE induced cysteinyl leucotrienes production in mast cells of patients with aspirin exacerbated respiratory disease.
abstract: BACKGROUND
  Aspirin causes bronchospasm in patients with aspirin exacerbated respiratory disease (AERD). The contribution of mast cells to the increased cysteinyl-leucotrienes (cys-LTs) detected in AERD patients is however not defined.
  
  
  OBJECTIVE
  Effects of prostaglandin (PG) E(2) and inhibitors of cyclooxygenase (COX) and lipoxygenase (LO) pathways on mediator release from cultured mast cells of normal subjects, aspirin tolerant asthma (ATA) and AERD patients were compared to better define the role of mast cells in AERD.
  
  
  METHODS
  Mast cells were cultured from peripheral blood progenitors and were activated by anti-IgE. Histamine, PGD(2) and cys-LTs released were then determined.
  
  
  RESULTS
  Basal release of all three mediators was similar in all subjects. Although the release of all three mediators was increased by anti-IgE, mast cells from AERD patients produced significantly more cys-LTs (6.9 +/- 2.0 ng/10(6) cells) than normal and ATA subjects (2.3 +/- 0.8 and 1.7 +/- 0.5 ng/10(6) cells, respectively). While COX and LO pathway inhibitors did not affect anti-IgE induced histamine release, they significantly suppressed the production of PGD(2) and cys-LTs, respectively, in all patients. PGE(2) significantly enhanced anti-IgE induced histamine and PGD(2) release from mast cells of normal subjects but not those of ATA and AERD patients. In contrast, PGE(2) suppressed only anti-IgE induced cys-LTs release from mast cells of AERD patients.
  
  
  CONCLUSIONS
  We speculate that overproduction of cys-LTs is unique to mast cells of AERD patients and is particularly sensitive to suppression by PGE(2). Consequently reduction of PGE(2) production by aspirin removes this endogenous control of cys-LTs overproduction, resulting in asthma attack.
authors.affiliation: Department of Pharmacology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: X S
authors.initials: XS
authors.lastname: Wang
authors.forename: A Y-Y
authors.initials: AY
authors.lastname: Wu
authors.forename: P S
authors.initials: PS
authors.lastname: Leung
authors.forename: H Y A
authors.initials: HY
authors.lastname: Lau
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D001241:Aspirin / Q000009:adverse effects*; D001986:Bronchial Spasm / Q000139:chemically induced; D002478:Cells, Cultured; D003545:Cysteine / Q000096:biosynthesis*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006632:Histamine / Q000096:biosynthesis; D006801:Humans; D007073:Immunoglobulin E; D015289:Leukotrienes / Q000096:biosynthesis*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D015230:Prostaglandin D2 / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000888:Antibodies, Anti-Idiotypic; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D007073:Immunoglobulin E; D006632:Histamine; D015232:Dinoprostone; D003545:Cysteine; D001241:Aspirin; D015230:Prostaglandin D2