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Effects of leukotriene receptor antagonists on monocyte chemotaxis, p38 and cytoplasmic calcium
Author(s) -
Hung ChihHsing,
Li ChiYuan,
Hua YiMing,
Chen ChunJung,
Yang Kuender D.,
Jong YuhJyh
Publication year - 2006
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/j.1399-3038.2006.00385.x
Subject(s) - monocyte , chemotaxis , medicine , peripheral blood mononuclear cell , zafirlukast , montelukast , immunology , receptor , biology , biochemistry , asthma , in vitro
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. [Ca 2+ ]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 μ m ) and zafirlukast (100 μ m ) 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 [Ca 2+ ]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 [Ca 2+ ]i and p38 MAPK expression.