title: Activation of human lung mast cells by monomeric immunoglobulin E.
abstract: The mechanism of chronic mast cell activation in asthma is unclear. Monomeric immunoglobulin (Ig)E in the absence of allergen induces mediator release from rodent mast cells, indicating a possible role for IgE in the continued activation of mast cells within the asthmatic bronchial mucosa. In this study it was investigated whether monomeric IgE induces Ca2+ influx and mediator release from human lung mast cells (HLMC). Purified HLMC were cultured for 4 weeks and then exposed to monomeric human myeloma IgE. Ratiometric Ca2+ imaging was performed on single fura-2-loaded cells. Histamine release was measured by radioenzymatic assay; leukotriene C4 (LTC4) and interleukin (IL)-8 were measured by ELISA. At concentrations experienced in vivo, monomeric IgE induced dose-dependent histamine release, LTC4 production and IL-8 synthesis. This was associated with a rise in cytosolic free Ca2+. Enhanced histamine release was still evident 1 week after initial exposure to IgE suggesting that continued exposure maintains enhanced secretion. Monomeric immunoglobulin E alone activates cultured human lung mast cells initiating Ca2+ influx, degranulation, arachidonic acid metabolism and cytokine synthesis. These findings support the hypothesis that immunoglobulin E loading of mast cells within the asthmatic airway contributes to the disordered airway physiology of this disease.
authors.affiliation: Institute for Lung Health, Dept of Infection, Immunity and Inflammation, University of Leicester, UK.
authors.forename: G
authors.initials: G
authors.lastname: Cruse
authors.forename: D
authors.initials: D
authors.lastname: Kaur
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: S M
authors.initials: SM
authors.lastname: Duffy
authors.forename: C E
authors.initials: CE
authors.lastname: Brightling
authors.forename: P
authors.initials: P
authors.lastname: Bradding
mesh_terms: D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D012016:Reference Values; D019089:Stem Cell Factor
chemical_list: D017077:Culture Media, Conditioned; D016209:Interleukin-8; D019089:Stem Cell Factor; D017997:Leukotriene C4; D007073:Immunoglobulin E; D006632:Histamine; D002118:Calcium