Montelukast inhibits neutrophil pro‐inflammatory activity by a cyclic AMP‐dependent mechanism

Background and purpose: The objective of this study was to characterize the effects of the cysteinyl leukotriene receptor antagonist, montelukast (0.1–2 µmol·L−1), on Ca2+‐dependent pro‐inflammatory activities, cytosolic Ca2+ fluxes and intracellular cAMP in isolated human neutrophils activated with the chemoattractants, N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine (1 µmol·L−1) and platelet‐activating factor (200 nmol·L−1). Experimental approach: Generation of reactive oxygen species was measured by lucigenin‐ and luminol‐enhanced chemiluminescence, elastase release by a colourimetric assay, leukotriene B4 and cAMP by competitive binding ELISA procedures, and Ca2+ fluxes by fura‐2/AM‐based spectrofluorimetric and radiometric (45Ca2+) procedures. Key results: Pre‐incubation of neutrophils with montelukast resulted in dose‐related inhibition of the generation of reactive oxygen species and leukotriene B4 by chemoattractant‐activated neutrophils, as well as release of elastase, all of which were maximal at 2 µmol·L−1 (mean percentages of the control values of 30 ± 1, 12 ± 3 and 21 ± 3 respectively; P