Levels of cysteinyl leukotriene receptor mRNA in human peripheral leucocytes: significantly higher expression of cysteinyl leukotriene receptor 2 mRNA in eosinophils

Background Cysteinyl leukotrienes (CysLTs) have been implicated as important contributors in the pathophysiology of asthma and their biological effects are mediated by at least two distinct G-protein-coupled receptors. cDNA sequences of cysteinyl leukotriene receptor 1 (CysLTR(1)) and cysteinyl leukotriene receptor 2 (CysLTR(2)) have recently been elucidated. Objectives Our aim is to explore gene expression and the comparative expression of CysLTR(1) mRNA and CysLTR(2) mRNA in human peripheral blood leucocytes. Methods Gene expression of CysLTR(1) and CysLTR(2) mRNAs in human peripheral blood eosinophils, neutrophils, monocytes and T lymphocytes has been measured by competitive reverse transcription-polymerase chain reactions using RNA or DNA competitors. Results (a) When cellular levels of CysLTR(1) mRNA were normalized to those of G3PDH mRNA, the relative concentration of CysLTR(1) mRNA in eosinophils (43.8 +/- 37.2, n=29) was significantly higher than that in neutrophils (18.7 +/- 23.3, n=11), monocytes (0.93 +/-1.1, n=10) and T lymphocytes (3.4 +/-2.4, n=11). (b) When measured using each DNA competitor, mRNAs for both types of CysLTR coexisted in each type of leucocyte. The ratio of CysLTR(1) mRNA to CysLTR(2) mRNA was significantly lower in eosinophils (0.65 +/-0.42, n=12) than in neutrophils (6.9 +/-4.9, n=12), monocytes (1.8 +/-0.9, n=10) and T lymphocytes (4.5 +/-5.7, n=10). (c) Human umbilical vein endothelial cells expressed CysLTR2 mRNA, but not CysLTR(1) mRNA. Conclusion These studies reveal that CysLTR(1) mRNA and, in particular, CysLTR(2) mRNA are abundantly expressed at high levels in eosinophils, raising the possibility that CysLTR may have an important physiological role in eosinophils and a CysLTR2 antagonist may be a good target for preventing signal transduction by CysLTs in eosinophils.