Activation of human lung mast cells by monomeric immunoglobulin E.
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.
Cruse
G
G
Institute for Lung Health, Dept of Infection, Immunity and Inflammation, University of Leicester, UK.
Kaur
D
D
Yang
W
W
Duffy
S M
SM
Brightling
C E
CE
Bradding
P
P
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
D017077:Culture Media, Conditioned; D016209:Interleukin-8; D019089:Stem Cell Factor; D017997:Leukotriene C4; D007073:Immunoglobulin E; D006632:Histamine; D002118:Calcium