Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation

Authors

  • Joshua A. Boyce

    Corresponding author
    1. Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
    2. Department of Medicine, Harvard Medical School, Boston, MA, USA.
    3. Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA, USA.
    4. Partners Asthma Center, Boston, MA, USA.
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Joshua A. Boyce, MD
Division of Rheumatology, Immunology and Allergy
Brigham and Women’s Hospital
Smith Research Building, Room 626
1 Jimmy Fund Way
Boston, MA 02115, USA
Tel.: 617-525-1261
Fax: 617-525-1260
E-mail: jboyce@rics.bwh.harvard.edu

Abstract

Summary:  When activated by specific antigen, complement, or other transmembrane stimuli, mast cells (MCs) generate three eicosanoids: prostaglandin (PG)D2, leukotriene (LT)B4, and LTC4, the parent molecule of the cysteinyl leukotrienes (cysLTs). These diverse lipid mediators, which are generated from a single cell membrane-associated precursor, arachidonic acid, can initiate, amplify, or dampen inflammatory responses and influence the magnitude, duration, and nature of subsequent immune responses. PGD2 and cysLTs, which were originally recognized for their bronchoconstricting and vasoactive properties, also serve diverse and pivotal functions in effector cell trafficking, antigen presentation, leukocyte activation, matrix deposition, and fibrosis. LTB4 is a powerful chemoattractant for neutrophils and certain lymphocyte subsets. Thus, MCs can contribute to each of these processes through eicosanoid generation. Additionally, MCs express G-protein-coupled receptors specific for cysLTs, LTB4, and another eicosanoid, PGE2. Each of these receptors can regulate MC functions in vivo by autocrine and paracrine mechanisms. This review focuses on the biologic functions for MC-associated eicosanoids, the regulation of their production, and the mechanisms by which eicosanoids may regulate MC function in host defense and disease.

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