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IgE-dependent release of leukotriene C4 from alveolar macrophages

Abstract

Slow reacting substances (SRS) are potent bronchoconstrictors that are thought to be important in the pathophysiology of asthma1. Human2–5 and animal6,7 lung fragments release SRS when sensitized by IgE antibody and challenged with specific antigen. SRS have been shown recently to be a family of peptidolipids called leukotrienes (LTC4, LTD4 and LTE4) that are derived from arachidonic acid8–11 and are potent bronchoconstrictors in vivo and in vitro12,14. It is not known which cell(s) is responsible for releasing SRS but two recent observations have directed our attention to alveolar macrophages. First, Capron and co-workers demonstrated that serum IgE antibody from rats immune to Schistosoma mansoni parasites could cause rat peritoneal macrophages to be cytotoxic for schistosomules in vitro15. This is a result of the interaction of IgE with macrophage IgE Fc receptors16. Similar receptors are also present on rat alveolar macrophages17. Second, Bach and Brashler18–21 established that rat peritoneal macrophages could release a mixture of LTC4 and LTD4 when stimulated by the calcium ionophore A23187. We now show that rat alveolar macrophages can be activated by calcium ionophore to release SRS and, when challenged with IgE antibody and specific antigen, release LTC4.

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Rankin, J., Hitchcock, M., Merrill, W. et al. IgE-dependent release of leukotriene C4 from alveolar macrophages. Nature 297, 329–331 (1982). https://doi.org/10.1038/297329a0

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