Cysteinyl leukotrienes and disease

Abstract

Cysteinyl leukotrienes (cys-LTs) are peptide-conjugated lipid inflammatory mediators generated pred minantly by hematopoietic effector cells. Although they were originally recognized based on their capacity to potently induce vascular leakage and smooth muscle contraction, they are now known to elicit a wide range of effects on hematopoietic and structural cells and to have a key role in the initiation and amplification of type 2 immunity and eosinophilic inflammation. The three ligands comprising the cys-LTs, that is, leukotriene (LT)C 4, LTD 4, and LTE 4, mediate their effects through at least three G protein-coupled receptors (GPCRs), termed the type 1 and type 2 cys-LT receptors (CysLT 1 R and CysLT 2 R, respectively), and the recently identified third receptor, GPR99, the only receptor with a binding preference for LTE 4. This chapter is concerned primarily with the expanding role of the cys-LTs and their receptors in asthma and aspirin-exacerbated respiratory disease, and touches on the potential implications for other pathobiological processes