Sepharose beads coated with
IgG stimulate eosinophils to produce
leukotriene C4 (
LTC4). This observation has been extended with specific immobilized
IgG/
antigen immune complexes to elicit mediator generation. An extract of Aspergillus fumigatus was covalently coupled to
Sepharose beads and incubated with the
IgG fraction of immune serum from patients with
allergic bronchopulmonary aspergillosis. These beads elicited generation of 7.72 +/- 1.7 pmol of
LTC4 immunoreactive material (n = 5) from 1 X 10(6) normal eosinophils of greater than 86% purity, and significantly less
LTC4 (0.73 +/- 0.19 pmol per 10(6) cells; n = 3) was produced by eosinophils after incubation with beads treated with
IgG from normal nonimmune serum. The maximum antibody-dependent release achieved represented approximately 20% of that induced by the
calcium ionophore (
A23187).
LTC4 was measured by radioimmunoassay and validated by reverse-phase high-performance liquid chromatography. The amount of
LTC4 generated was dependent on the concentration of A. fumigatus-specific
IgG, and mediator release was completely abolished by prior adsorption of the
IgG fraction onto
Sepharose-
protein A (Staphylococcus aureus). Grass pollen-specific
IgG antibody/
antigen complexes, in combination with
Sepharose beads, also triggered generation of
LTC4 immunoreactive material. There was no evidence to suggest that
IgE/A. fumigatus
immune complexes triggered
LTC4 generation, although
IgE myeloma
protein, in association with
Sepharose beads, was a weak stimulus. The efficacy of the
IgG immune complex-dependent stimulation of eosinophils suggests a possible physiologic mechanism whereby these cells could participate in the inflammatory changes associated with
allergic bronchopulmonary aspergillosis and similar allergic disorders.