Eicosanoids as Regulators of Eicosanoid Release in Macrophages: Impact for Exacerbation of Tissue Damage by Non-Steroidal Anti-Inflammatory Drugs

  • Iván L. Bonta
  • Graham R. Elliott
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 177)


Macrophages are an important source of eicosanoids, releasing both cyclooxygenase and lipoxygenase metabolites of arachidonic acid (AA). Macrophages are also equipped with receptors for these essential fatty acid products. Hence eicosanoids released from macrophages not only influence the activity of surrounding cells but also modify the state of activation of the macrophage itself. Previous studies have shown that both, leukotrienes (LTs), which are metabolites of the lipoxygenase pathway, and cyclooxygenase inhibitors activate macrophages, whilst PGE2, a cyclooxygenase metabolite, suppresses cell activation as indicated by the release of lysosomal enzymes. LTC4 has been shown to stimulate PGE2 synthesis, indicating that the action of this mediator is self-limiting and that eicosanoid formation is partially regulated by interactions between the different metabolites. These earlier findings prompted us to further investigate the possibility that PGE2 suppresses, and cyclooxygenase inhibitors stimulate, macrophage functions via effects on LT synthesis. In this article, besides reviewing the most salient previous observations, account of recent experiments on the modulation of this synthesis by PGE2 and non-steroidal anti-inflammatory drugs (NSAIDs) will be given. Most of the work is now in the process of publication in extenso (Elliott et al. 1988) and therefore, in the present article several technical details are omitted. While the regulatory role of PGE2 on macrophage functions is an earlier proposal (Bonta & Parnham 1982), presently the focus of discussion will be on the balance between synthesis of lipoxygenase metabolites and PGE2, which maintains the macrophage in a dynamic state.


Lysosomal Enzyme Cyclooxygenase Inhibitor Suppress Cell Activation Lipoxygenase Metabolite Eicosanoid Formation 
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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Iván L. Bonta
    • 1
  • Graham R. Elliott
    • 1
  1. 1.Department of Pharmacology, Faculty of MedicineErasmus University RotterdamRotterdamThe Netherlands

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