Effects of leukotriene receptor antagonists on monocyte chemotaxis, p38 and cytoplasmic calcium.

Montelukast and zafirlukast, two cysteinyl leukotriene receptor antagonists (LTRAs), have been shown to have a beneficial effect on the clinical symptoms of asthma. LTRAs can inhibit eosinophil recruitment; however, little is known about their role in monocyte migration. We investigated whether montelukast and zafirlukast could suppress chemokine-induced chemotaxis of monocytes and signaling. Chemotaxis of monocytes from peripheral blood mononuclear cells (PBMCs), cord blood mononuclear cells (CBMCs), and THP-1 cells was evaluated using a 24-well transwell microchamber. [Ca2+]i was measured with the fluorescence calcium indicator fura-2/AM photometry system. p38 MAPK expression was measured by Western blotting. Results showed that montelukast (1-100 microm) and zafirlukast (100 microm) significantly down-regulated monocyte chemoattractant protein-1(MCP-1)-induced chemotaxis of THP-1 cells and human primary monocytes from PBMCs and CBMCs (p<0.05, each comparison). Montelukast also abolished MCP-1-induced [Ca2+]i and pp38 MAPK expression in THP-1 cells in a dose-dependent manner. These data demonstrate that montelukast is effective in down-regulating human monocyte chemotaxis induced by MCP-1. This effect may involve the down-regulation of MCP-1-induced [Ca2+]i and p38 MAPK expression.