A tale of two CysLTs

James, Anna J. and Sampson, A. P. (2001) A tale of two CysLTs. Clinical Exp Allergy, 31 (11), 1660-1664. (doi:10.1046/j.1365-2222.2001.01259.x).

Abstract

The importance of the cysteinyl-leukotrienes (cysLTs) LTC4, LTD4 and LTE4 as mediators of asthma is now widely recognized [1]. Their biological actions, including bronchoconstriction, microvascular oedema, mucus hypersecretion and eosinophil chemotaxis, are mediated by CysLT type 1 (CysLT1) and type 2 (CysLT2) receptors distinct from those for LTB4, the sole member of a separate branch of the leukotriene family. CysLT1 is the molecular target of the leukotriene receptor antagonists montelukast, pranlukast and zafirlukast that have entered international asthma treatment guidelines since their introduction in many countries in 1997. These drugs do not block CysLT2 and the actions of cysLTs mediated by the type 2 receptor remain poorly defined. Although cys-LT receptor subtypes were first identified pharmacologically, the recent cloning and molecular characterization of both receptors [2-5] represents an important advance in defining their respective roles in airway inflammation. In particular, the ability of the oral CysLT1 antagonists to reduce eosinophilia in the blood and airways of asthmatic patients over a period of weeks [6] points to an important role of cysLTs and CysLT1 receptors in regulating eosinophil migration, proliferation, or apoptosis. The current issue of Clinical & Experimental Allergy contains an intriguing report by Dr Mita and colleagues from the National Sagamihara Hospital in Kanagawa, Japan, indicating that human eosinophils in fact express greater amounts of mRNA for the CysLT2 receptor than for CysLT1[7]. This raises the interesting possibility that the CysLT2 receptor may mediate important aspects of eosinophil behaviour. This review will survey current information on the two cysLT receptor subtypes and examine the evidence for their relative contribution to inflammatory processes.

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Contributors

Author: A. P. Sampson

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