IgE and IgG are synergistic in antigen-mediated release of thromboxane from human lung macrophages.
The mechanism of IgE-mediated release of thromboxane A2 from human lung macrophages has been studied using a monoclonal chimeric human/mouse IgE antibody and its specific antigen. The cells could be sensitized at 37 degrees C but not at 4 degrees C by incubation with IgE, and released a significant amount of thromboxane A2 (TXA2), measured as the stable hydrolysis product TXB2, in response to an anti-chimeric IgE antibody. In contrast, stimulation of IgE-sensitized macrophages with the specific antigen produced less than 10% of this response. A similar time course for the release of TXB2 and the formation of inositol monophosphate in the presence of LiCl was observed. Cleavage of the Fc domain of the anti-chimeric IgE antibody substantially eliminated its capacity to stimulate IgE-sensitized cells. However, the weak or undetectable response to chimeric IgE plus specific antigen was substantially potentiated by an antigen-specific chimeric IgG antibody. IgG-sensitized macrophages did not respond to antigen challenge by the release of TXB2. Preincubation of the cells with a monoclonal antibody against the low affinity receptor for IgE (Fc epsilon RII/CD23) did not prevent IgE sensitization. We conclude that cell-bound IgE antibody cannot induce the release of TXB2 but has fixed antigen which then must interact with specific IgG antibody and IgG receptors to induce mediator release.
Storch
J
J
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, United Kingdom.
MacDermot
J
J
D000936:Antigen-Antibody Complex / Q000276:immunology*; D000943:Antigens, Differentiation / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid; D006801:Humans; D007073:Immunoglobulin E / Q000008:administration & dosage*; D007074:Immunoglobulin G / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D011940:Receptor Aggregation; D011961:Receptors, Fc / Q000276:immunology / Q000502:physiology; D017455:Receptors, IgE; D017452:Receptors, IgG; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism
D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG; D007073:Immunoglobulin E; D013929:Thromboxane B2; D013928:Thromboxane A2