Thromboxane release by lymphokine-differentiated U937 human monocytic cells: response to platelet-activating factor (PAF) and chemotactic peptide (FMLP) but not to low affinity IGE-receptor (Fc epsilon RII/CD23) occupation.
The primary objective of this study was to explore if the CD23 antigen is a functional low affinity IgE receptor on macrophages for the release of thromboxane B2 (TXB2). The responsiveness of U937 monocytic cells and their macrophage-like inducible forms to platelet-activating factor (Paf), the chemotactic peptide fMLP, and low affinity IgE-receptor occupation was examined. Differentiation of U937 cells by phorbol myristate acetate (PMA) and a cancer cell line (HBT 5637) conditioned medium (5637-CM), but not INFg or IL4, resulted in a macrophage-like cell line which released TXB2. A high basal release of TXB2 with no significant response to Paf or fMLP challenge was seen following culture of cells with PMA. In 5637-CM-differentiated cells, Paf and fMLP induced a rapid release of TXB2, about 10 fold above basal activity. There was a slow Ca-independent response to short-term treatment with PMA and a rapid Ca-dependent response to the ionophore A23187. Both stimulants acted synergistically on TXB2 synthesis in 5637-CM differentiated cells. Although low affinity receptors for IgE (Fc epsilon RII/CD23) were induced by 5637-CM, no TXB2 was released in response to soluble or latex-bound IgE-antigen complexes or to anti-Fc epsilon RII/CD23-antibodies. IL4 and to a lesser extent INFg both induced Fc epsilon RII/CD23 receptor expression, but inhibited release of TXB2 in response to Paf, fMLP, or PMA. We conclude that the functional receptors for IgE on mature macrophages are most probably not Fc epsilon RII/CD23.
Storch
J
J
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
Edwards
R J
RJ
MacDermot
J
J
D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008222:Lymphokines / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D011961:Receptors, Fc / Q000378:metabolism / Q000502:physiology; D017455:Receptors, IgE; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
D000888:Antibodies, Anti-Idiotypic; D000944:Antigens, Differentiation, B-Lymphocyte; D008222:Lymphokines; D010972:Platelet Activating Factor; D011961:Receptors, Fc; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D015847:Interleukin-4; D007073:Immunoglobulin E; D000001:Calcimycin; D013929:Thromboxane B2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate