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

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.