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


CONCLUSIONS
The inhibitory effect of pranlukast on eosinophil transmigration is highly specific for the CysLT1-dependent pathway.
Nagata
Makoto
M
Department of Respiratory Medicine, Saitama Medical School, Japan. favre4mn@saitama-med.ac.jp
Saito
Keiko
K
Kikuchi
Izumi
I
Hagiwara
Koichi
K
Kanazawa
Minoru
M
D000328:Adult; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology*; D004347:Drug Interactions; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D010972:Platelet Activating Factor / Q000494:pharmacology; D018077:Receptors, Leukotriene
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D002867:Chromones; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D010972:Platelet Activating Factor; D018077:Receptors, Leukotriene; D017998:Leukotriene D4; C083169:leukotriene D4 receptor; C047681:pranlukast