Roles of cysteinyl leukotrienes and their receptors in immune cell-related functions

Yoshihide Kanaoka; K Frank Austen

doi:10.1016/bs.ai.2019.04.002

Roles of cysteinyl leukotrienes and their receptors in immune cell-related functions

Adv Immunol. 2019:142:65-84. doi: 10.1016/bs.ai.2019.04.002. Epub 2019 May 14.

Authors

Yoshihide Kanaoka¹, K Frank Austen²

Affiliations

¹ Department of Medicine, Harvard Medical School and Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, United States. Electronic address: [email protected].
² Department of Medicine, Harvard Medical School and Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, United States. Electronic address: [email protected].

PMID: 31296303
DOI: 10.1016/bs.ai.2019.04.002

Abstract

The cysteinyl leukotrienes (cys-LTs), leukotriene C₄, (LTC₄), LTD₄, and LTE₄, are lipid mediators of inflammation. LTC₄ is the only intracellularly synthesized cys-LT through the 5-lipoxygenase and LTC₄ synthase pathway and after transport is metabolized to LTD₄ and LTE₄ by specific extracellular peptidases. Each cys-LT has a preferred functional receptor in vivo; LTD₄ to the type 1 cys-LT receptor (CysLT₁R), LTC₄ to CysLT₂R, and LTE₄ to CysLT₃R (OXGR1 or GPR99). Recent studies in mouse models revealed that there are multiple regulatory mechanisms for these receptor functions and each receptor plays a distinct role as observed in different mouse models of inflammation and immune responses. This review focuses on the integrated host responses to the cys-LT/CysLTR pathway composed of sequential ligands with preferred receptors as seen from mouse models. It also discusses potential therapeutic targets for LTC₄ synthase, CysLT₂R, and CysLT₃R.

Keywords: Animal models; Arachidonic acid; Epithelial cells; G protein-coupled receptors; Hematopoietic cells; Inflammation; Lipid mediators; Membrane proteins.

Publication types

Review

MeSH terms

5-Lipoxygenase-Activating Proteins / genetics
5-Lipoxygenase-Activating Proteins / metabolism
Animals
Arachidonate 5-Lipoxygenase / genetics
Arachidonate 5-Lipoxygenase / metabolism
Asthma, Aspirin-Induced / immunology
Asthma, Aspirin-Induced / metabolism
Cysteine / biosynthesis
Cysteine / chemistry
Cysteine / metabolism
Cysteine / physiology*
Dipeptidases / genetics
Dipeptidases / metabolism
Glutathione Transferase / genetics
Glutathione Transferase / metabolism
Group IV Phospholipases A2 / genetics
Group IV Phospholipases A2 / metabolism
Humans
Inflammation / immunology*
Inflammation / metabolism
Leukotriene C4 / biosynthesis
Leukotriene C4 / chemistry
Leukotriene C4 / metabolism
Leukotriene C4 / physiology*
Leukotriene E4 / biosynthesis
Leukotriene E4 / chemistry
Leukotriene E4 / metabolism
Leukotriene E4 / physiology*
Leukotrienes / biosynthesis
Leukotrienes / chemistry
Leukotrienes / metabolism
Leukotrienes / physiology*
Mice
Neoplasms / genetics
Neoplasms / immunology
Neoplasms / metabolism
Receptors, Leukotriene / genetics
Receptors, Leukotriene / immunology*
Receptors, Leukotriene / metabolism

Substances

5-Lipoxygenase-Activating Proteins
Leukotrienes
Receptors, Leukotriene
cysteinyl-leukotriene
Leukotriene C4
Leukotriene E4
Arachidonate 5-Lipoxygenase
Glutathione Transferase
Group IV Phospholipases A2
Dipeptidases
leukotriene-C4 synthase
Cysteine
leukotriene D4 receptor