Interaction of suplatast tosilate (IPD) with chloride channels in human blood eosinophils

A potential mechanism underlying its anti-allergic and anti-asthmatic effects

Devendra K. Agrawal, G. Cheng, M. J. Kim, M. Kiniwa

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Introduction: Alterations in chloride ion channels have been implicated in the induction of changes in cell shape and volume. Because blood and tissue eosinophilia are hallmarks of bronchial asthma, in this study we examined the role of chloride channels in the underlying effects of suplatast tosilate (IPD), an anti-allergic drug, in human blood eosinophils. Methods: Eosinophils were isolated and purified from the blood of allergic asthmatic donors. Chloride ion currents were recorded using the whole-cell patch-clamp technique in freshly isolated eosinophils. The current-voltage relationship of whole-cell currents in human blood eosinophils was calculated and recorded. The effect of chloride channel blockers was examined on superoxide release, eosinophil chemotaxis as measured by the Boyden chamber, and eosinophil adhesion to endothelial cells. Radioligand binding studies with [3H]IPD and competition curves with chloride channel blockers were performed. Results: IPD increased both inward and outward chloride currents in human blood eosinophils. IPD in 1 ng/mL did not have significant effect on chloride current. However, at 5 ng/mL IPD activated both outward and inward currents in human blood eosinophils. Chloride channel blockers inhibited IPD-induced respiratory burst in eosinophils, eosinophil chemotaxis, and eosinophil adhesion to endothelial cells. All these effects of IPD on chloride current and the resultant functional responses in human blood eosinophils were not due to its basic salt, p-toluenesulphonic acid monohydrate. Human blood eosinophils contained specific binding sites for [3H]IPD with KD and Bmax values of 187.7±105.8 nm and 58.7±18.7 fmol/106 cells, respectively. Both NPPB and DIDS competed, in a dose-dependent manner, for the specific binding of [ 3H]IPD in human blood eosinophils. Conclusion: These data suggest that the anti-allergic and anti-asthmatic effects of IPD could be due to its interaction with chloride channels in human blood eosinophils.

Original languageEnglish
Pages (from-to)305-312
Number of pages8
JournalClinical and Experimental Allergy
Volume38
Issue number2
DOIs
StatePublished - Feb 2008

Fingerprint

Anti-Asthmatic Agents
Anti-Allergic Agents
Chloride Channels
Eosinophils
Chlorides
suplatast tosilate
Chemotaxis
Endothelial Cells
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Respiratory Burst
Cell Shape
Eosinophilia
Patch-Clamp Techniques

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

@article{4bebb564cf8a4953bc4a8466c866b1e3,
title = "Interaction of suplatast tosilate (IPD) with chloride channels in human blood eosinophils: A potential mechanism underlying its anti-allergic and anti-asthmatic effects",
abstract = "Introduction: Alterations in chloride ion channels have been implicated in the induction of changes in cell shape and volume. Because blood and tissue eosinophilia are hallmarks of bronchial asthma, in this study we examined the role of chloride channels in the underlying effects of suplatast tosilate (IPD), an anti-allergic drug, in human blood eosinophils. Methods: Eosinophils were isolated and purified from the blood of allergic asthmatic donors. Chloride ion currents were recorded using the whole-cell patch-clamp technique in freshly isolated eosinophils. The current-voltage relationship of whole-cell currents in human blood eosinophils was calculated and recorded. The effect of chloride channel blockers was examined on superoxide release, eosinophil chemotaxis as measured by the Boyden chamber, and eosinophil adhesion to endothelial cells. Radioligand binding studies with [3H]IPD and competition curves with chloride channel blockers were performed. Results: IPD increased both inward and outward chloride currents in human blood eosinophils. IPD in 1 ng/mL did not have significant effect on chloride current. However, at 5 ng/mL IPD activated both outward and inward currents in human blood eosinophils. Chloride channel blockers inhibited IPD-induced respiratory burst in eosinophils, eosinophil chemotaxis, and eosinophil adhesion to endothelial cells. All these effects of IPD on chloride current and the resultant functional responses in human blood eosinophils were not due to its basic salt, p-toluenesulphonic acid monohydrate. Human blood eosinophils contained specific binding sites for [3H]IPD with KD and Bmax values of 187.7±105.8 nm and 58.7±18.7 fmol/106 cells, respectively. Both NPPB and DIDS competed, in a dose-dependent manner, for the specific binding of [ 3H]IPD in human blood eosinophils. Conclusion: These data suggest that the anti-allergic and anti-asthmatic effects of IPD could be due to its interaction with chloride channels in human blood eosinophils.",
author = "Agrawal, {Devendra K.} and G. Cheng and Kim, {M. J.} and M. Kiniwa",
year = "2008",
month = "2",
doi = "10.1111/j.1365-2222.2007.02877.x",
language = "English",
volume = "38",
pages = "305--312",
journal = "Clinical and Experimental Allergy",
issn = "0954-7894",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Interaction of suplatast tosilate (IPD) with chloride channels in human blood eosinophils

T2 - A potential mechanism underlying its anti-allergic and anti-asthmatic effects

AU - Agrawal, Devendra K.

AU - Cheng, G.

AU - Kim, M. J.

AU - Kiniwa, M.

PY - 2008/2

Y1 - 2008/2

N2 - Introduction: Alterations in chloride ion channels have been implicated in the induction of changes in cell shape and volume. Because blood and tissue eosinophilia are hallmarks of bronchial asthma, in this study we examined the role of chloride channels in the underlying effects of suplatast tosilate (IPD), an anti-allergic drug, in human blood eosinophils. Methods: Eosinophils were isolated and purified from the blood of allergic asthmatic donors. Chloride ion currents were recorded using the whole-cell patch-clamp technique in freshly isolated eosinophils. The current-voltage relationship of whole-cell currents in human blood eosinophils was calculated and recorded. The effect of chloride channel blockers was examined on superoxide release, eosinophil chemotaxis as measured by the Boyden chamber, and eosinophil adhesion to endothelial cells. Radioligand binding studies with [3H]IPD and competition curves with chloride channel blockers were performed. Results: IPD increased both inward and outward chloride currents in human blood eosinophils. IPD in 1 ng/mL did not have significant effect on chloride current. However, at 5 ng/mL IPD activated both outward and inward currents in human blood eosinophils. Chloride channel blockers inhibited IPD-induced respiratory burst in eosinophils, eosinophil chemotaxis, and eosinophil adhesion to endothelial cells. All these effects of IPD on chloride current and the resultant functional responses in human blood eosinophils were not due to its basic salt, p-toluenesulphonic acid monohydrate. Human blood eosinophils contained specific binding sites for [3H]IPD with KD and Bmax values of 187.7±105.8 nm and 58.7±18.7 fmol/106 cells, respectively. Both NPPB and DIDS competed, in a dose-dependent manner, for the specific binding of [ 3H]IPD in human blood eosinophils. Conclusion: These data suggest that the anti-allergic and anti-asthmatic effects of IPD could be due to its interaction with chloride channels in human blood eosinophils.

AB - Introduction: Alterations in chloride ion channels have been implicated in the induction of changes in cell shape and volume. Because blood and tissue eosinophilia are hallmarks of bronchial asthma, in this study we examined the role of chloride channels in the underlying effects of suplatast tosilate (IPD), an anti-allergic drug, in human blood eosinophils. Methods: Eosinophils were isolated and purified from the blood of allergic asthmatic donors. Chloride ion currents were recorded using the whole-cell patch-clamp technique in freshly isolated eosinophils. The current-voltage relationship of whole-cell currents in human blood eosinophils was calculated and recorded. The effect of chloride channel blockers was examined on superoxide release, eosinophil chemotaxis as measured by the Boyden chamber, and eosinophil adhesion to endothelial cells. Radioligand binding studies with [3H]IPD and competition curves with chloride channel blockers were performed. Results: IPD increased both inward and outward chloride currents in human blood eosinophils. IPD in 1 ng/mL did not have significant effect on chloride current. However, at 5 ng/mL IPD activated both outward and inward currents in human blood eosinophils. Chloride channel blockers inhibited IPD-induced respiratory burst in eosinophils, eosinophil chemotaxis, and eosinophil adhesion to endothelial cells. All these effects of IPD on chloride current and the resultant functional responses in human blood eosinophils were not due to its basic salt, p-toluenesulphonic acid monohydrate. Human blood eosinophils contained specific binding sites for [3H]IPD with KD and Bmax values of 187.7±105.8 nm and 58.7±18.7 fmol/106 cells, respectively. Both NPPB and DIDS competed, in a dose-dependent manner, for the specific binding of [ 3H]IPD in human blood eosinophils. Conclusion: These data suggest that the anti-allergic and anti-asthmatic effects of IPD could be due to its interaction with chloride channels in human blood eosinophils.

UR - http://www.scopus.com/inward/record.url?scp=38349153328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38349153328&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2222.2007.02877.x

DO - 10.1111/j.1365-2222.2007.02877.x

M3 - Article

VL - 38

SP - 305

EP - 312

JO - Clinical and Experimental Allergy

JF - Clinical and Experimental Allergy

SN - 0954-7894

IS - 2

ER -