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Lipoxygenase products modulate histamine release in human basophils

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Abstract

Arachidonic acid released from cellular phospholipids is metabolized by two major enzyme systems1. The cyclo-oxygenase pathways are responsible for the production of prostaglandins, thromboxanes and prostacyclin while the lipoxygenase pathways form a series of monoperoxy- and monohydroxyeicosatetraenoic acids. The 5-lipoxygenase pathway eventually leads to the production of both leukotriene B, one of the most potent chemotactic molecules known, and SRS-A (slow-reacting substance of anaphylaxis—leukotrienes C and D). Our earlier studies of the lipoxygenase enzyme(s) suggested that a product (s) of lipoxygenase (s) is both necessary for histamine release from human basophils and blunts endogenous control mechanisms2–4. To test this hypothesis, we have studied the effect of exogenously added products of lipoxygenase pathways on antigen-induced histamine release from human basophilic leukocytes in vitro. The present report demonstrates that 5-hydroperoxyeicosatetraenoic acid (5-HPETE), at sub-micromolar concentrations, causes both a dose-dependent enhancement of histamine release and a reversal of the inhibition of histamine release caused by hormones and other agonists which act via adenylate cyclase. The reduced product of 5-HPETE, 5-hydroxyeicosatetraenoic acid (5-HETE) has both activities, but is approximately 3 to 10 times less potent.

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Authors and Affiliations

  1. The Johns Hopkins University School of Medicine, Department of Medicine, Divisions of Clinical Immunology and Pulmonary Medicine, Baltimore, Maryland, 21239

    Stephen P. Peters, Marvin I. Siegel, Anne Kagey-Sobotka & Lawrence M. Lichtenstein

  2. Burroughs Wellcome Co., Research Triangle Park, North Carolina, 27709, USA

    Stephen P. Peters, Marvin I. Siegel, Anne Kagey-Sobotka & Lawrence M. Lichtenstein

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  1. Stephen P. Peters
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  2. Marvin I. Siegel
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  3. Anne Kagey-Sobotka
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  4. Lawrence M. Lichtenstein
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Peters, S., Siegel, M., Kagey-Sobotka, A. et al. Lipoxygenase products modulate histamine release in human basophils. Nature 292, 455–457 (1981). https://doi.org/10.1038/292455a0

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