Effect of the cysteinyl leukotriene antagonist pranlukast on transendothelial migration of eosinophils

Int Arch Allergy Immunol. 2005:137 Suppl 1:2-6. doi: 10.1159/000085424. Epub 2005 Jun 2.

Abstract

Background: Evidence shows that leukotriene receptor antagonist (LTRA) can cause a partial reduction of eosinophils in the asthmatic airway. Although cysteinyl leukotrienes (CysLTs) can regulate the development of eosinophilic inflammation, LTRA might modulate the eosinophilic response to other inflammatory molecules involved in allergic inflammation. Montelukast is an LTRA that inhibits eosinophil transendothelial migration (TEM) in response to platelet-activating factor (PAF). The present study evaluates whether pranlukast (an LTRA) modifies eosinophil TEM in response to chemoattractants including PAF and C-C chemokines.

Methods: Eosinophils isolated from the blood of healthy individuals were incubated with or without pranlukast. We then evaluated eosinophil transmigration across human umbilical vein endothelial cells in response to LTD(4), eotaxin, RANTES and PAF.

Results: Pranlukast did not modify the spontaneous transmigration of eosinophils (n = 5). As reported, eosinophil TEM was significantly augmented by 0.1 microM LTD(4) and this enhancement was blocked by 1 microM pranlukast (p < 0.001; n = 6). On the other hand, pranlukast did not modify eosinophil transmigration in response to eotaxin, RANTES, or PAF (p > 0.1; n = 5).

Conclusion: The inhibitory effect of pranlukast on eosinophil transmigration is highly specific for the CysLT1-dependent pathway.

MeSH terms

  • Adult
  • Cell Movement / drug effects*
  • Cell Movement / immunology
  • Chemokine CCL11
  • Chemokine CCL5 / pharmacology
  • Chemokines, CC / pharmacology
  • Chromones / pharmacology*
  • Drug Interactions
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Eosinophils / cytology
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Female
  • Humans
  • Leukotriene Antagonists / pharmacology*
  • Leukotriene D4 / pharmacology
  • Male
  • Membrane Proteins / antagonists & inhibitors*
  • Platelet Activating Factor / pharmacology
  • Receptors, Leukotriene

Substances

  • CCL11 protein, human
  • Chemokine CCL11
  • Chemokine CCL5
  • Chemokines, CC
  • Chromones
  • Leukotriene Antagonists
  • Membrane Proteins
  • Platelet Activating Factor
  • Receptors, Leukotriene
  • Leukotriene D4
  • leukotriene D4 receptor
  • pranlukast