title: Montelukast inhibits leukotriene stimulation of human dendritic cells in vitro.
abstract: BACKGROUND
  Leukotrienes are potent inflammatory mediators which modulate immune responses and induce bronchoconstriction in susceptible individuals. Montelukast (MK) is a leukotriene receptor (CysLT1) antagonist that has been shown to prevent exacerbation of asthma. Considering the plethora of potential cellular targets for MK, specific mechanisms for its therapeutic action are still not fully understood. In vitro, we determined whether human dendritic cell function could be affected by leukotriene C(4) (LTC(4)) treatment and whether MK had potential in modulating this response. We also studied the effect of LTC(4) in the context of response to an airway virus (respiratory syncytial virus, RSV).
  
  
  METHODS
  Human monocyte-derived dendritic cells (moDCs) exposed to LTC(4), MK, or both, were cocultured with autologous T cells, with or without RSV. The effects of LTC(4) and MK on cell function were determined by ELISA and proliferation assays.
  
  
  RESULTS
  Both moDCs and their precursors--monocytes--express LTC(4) receptor CysLT1, making them potential targets for MK. moDCs cultured with LTC(4) release the eosinophil chemoattractant RANTES (CCL5) and induce greater T cell proliferation. Both were blocked by the presence of MK. MK treatment, albeit anti-inflammatory, did not interfere with the moDC-dependent T cell-proliferative responses induced by RSV.
  
  
  CONCLUSIONS
  LTC(4), chronically present in the airways of asthma patients, could induce an exaggerated inflammatory response to airway infection via dendritic cell activation, which would be prevented by MK. Our study provides additional insight into the mechanisms of action of this leukotriene receptor antagonist.
authors: Pulmonary Research Group, Departments of Pediatrics, University of Alberta, Edmonton, Alta., Canada.
authors: Ramses
authors: R
authors: Ilarraza
authors: Yingqi
authors: Y
authors: Wu
authors: Darryl J
authors: DJ
authors: Adamko
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003521:Cyclopropanes; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D006801:Humans; D017997:Leukotriene C4 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D061251:Primary Cell Culture; D011804:Quinolines / Q000494:pharmacology*; D018077:Receptors, Leukotriene / Q000276:immunology / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D013440:Sulfides; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D018946:Chemokine CCL5; D003521:Cyclopropanes; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; C083173:leukotriene C4 receptor; D017997:Leukotriene C4; C083169:leukotriene D4 receptor; C093875:montelukast