Effect of a specific cysteinyl leukotriene-receptor 1-antagonist (montelukast) on the transmigration of eosinophils across human umbilical vein endothelial cells.
BACKGROUND
Leukotrienes have been implicated in the selective infiltration of eosinophils into the bronchial mucosa in asthma.


OBJECTIVE
We studied whether eosinophil transmigration through cultured human umbilical vein endothelial cells (HUVECs) can be blocked by a specific cysteinyl LT1-receptor-antagonist.


METHODS
Unstimulated and stimulated eosinophils from patients with asthma and normal controls were subjected to confluent human umbilical vein endothelial cell (HUVEC) monolayers separating the upper and lower chamber of Transwell culture plates. Unstimulated eosinophils or cells pre-incubated in the presence of the eosinophil activating cytokines GM-CSF or IL-13 were placed in the upper chambers while PAF, a potent chemoattractant factor for eosinophils, was added to the lower chamber. Migration of eosinophils was quantified by a beta-glucuronidase assay.


RESULTS
The assumption that eosinophils express CysLT1 (cysteinyl-leukotriene 1)-receptors was based on our demonstration of mRNA-expression for the CysLT-1-receptor by polymerase chain reaction on purified eosinophils. The chemotactic response to PAF was significantly reduced when eosinophils were pre-incubated with montelukast for 15 min. When eosinophils were pre-incubated with GM-CSF and/or IL-13, the migratory response to PAF was also significantly reduced by montelukast.


CONCLUSIONS
From these data we conclude that the specific cysteinyl LT1-receptor antagonist montelukast can inhibit PAF-induced eosinophil transmigration through cultured HUVEC monolayers.
Virchow
J C
JC
Abteilung für Pneumologie, Universitätsklinikum Freiburg, Freiburg, Germany. Virchow@med1.UKL.UNI-FREIBURG.DE
Faehndrich
S
S
Nassenstein
C
C
Bock
S
S
Matthys
H
H
Luttmann
W
W
D000085:Acetates / Q000037:antagonists & inhibitors*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000037:antagonists & inhibitors*; D001249:Asthma / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003521:Cyclopropanes; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins; D010972:Platelet Activating Factor / Q000187:drug effects / Q000502:physiology; D011804:Quinolines / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000235:genetics; D018077:Receptors, Leukotriene / Q000235:genetics; D012680:Sensitivity and Specificity; D013440:Sulfides; D014471:Umbilical Veins / Q000166:cytology* / Q000187:drug effects*
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D018793:Interleukin-13; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D010972:Platelet Activating Factor; D011804:Quinolines; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; D013440:Sulfides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor; C093875:montelukast