The antibacterial activity of human neutrophils and eosinophils requires proton channels but not BK channels

Jon K. Femling, Vladimir V. Cherny, Deri Morgan, Balázs Rada, A. Paige Davis, Gabor Czirják, Peter Enyedi, Sarah K. England, Jessica G. Moreland, Erzsébet Ligeti, William M. Nauseef, Thomas E. DeCoursey

Research output: Contribution to journalArticle

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Abstract

Electrophysiological events are of central importance during the phagocyte respiratory burst, because NADPH oxidase is electrogenic and voltage sensitive. We investigated the recent suggestion that large-conductance, calcium-activated K+ (BK) channels, rather than proton channels, play an essential role in innate immunity (Ahluwalia, J., A. Tinker, L.H. Clapp, M.R. Duchen, A.Y. Abramov, S. Page, M. Nobles, and A.W. Segal. 2004. Nature. 427:853-858). In PMA-stimulated human neutrophils or eosinophils, we did not detect BK currents, and neither of the BK channel inhibitors iberiotoxin or paxilline nor DPI inhibited any component of outward current. BK inhibitors did not inhibit the killing of bacteria, nor did they affect NADPH oxidase-dependent degradation of bacterial phospholipids by extracellular gIIA-PLA2 or the production of superoxide anion (O2.-). Moreover, an antibody against the BK channel did not detect immunoreactive protein in human neutrophils. A required role for voltage-gated proton channels is demonstrated by Zn 2+ inhibition of NADPH oxidase activity assessed by H 2O2 production, thus validating previous studies showing that Zn2+ inhibited O2.- production when assessed by cytochrome c reduction. In conclusion, BK channels were not detected in human neutrophils or eosinophils, and BK inhibitors did not impair antimicrobial activity. In contrast, we present additional evidence that voltage-gated proton channels serve the essential role of charge compensation during the respiratory burst.

Original languageEnglish
Pages (from-to)659-672
Number of pages14
JournalJournal of General Physiology
Volume127
Issue number6
DOIs
Publication statusPublished - Jun 2006

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Large-Conductance Calcium-Activated Potassium Channels
Eosinophils
Human Activities
Protons
NADPH Oxidase
Neutrophils
Respiratory Burst
Calcium-Activated Potassium Channels
Phagocytes
Cytochromes c
Innate Immunity
Superoxides
Phospholipids
Bacteria
Antibodies
Proteins

ASJC Scopus subject areas

  • Physiology

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The antibacterial activity of human neutrophils and eosinophils requires proton channels but not BK channels. / Femling, Jon K.; Cherny, Vladimir V.; Morgan, Deri; Rada, Balázs; Davis, A. Paige; Czirják, Gabor; Enyedi, Peter; England, Sarah K.; Moreland, Jessica G.; Ligeti, Erzsébet; Nauseef, William M.; DeCoursey, Thomas E.

In: Journal of General Physiology, Vol. 127, No. 6, 06.2006, p. 659-672.

Research output: Contribution to journalArticle

Femling, JK, Cherny, VV, Morgan, D, Rada, B, Davis, AP, Czirják, G, Enyedi, P, England, SK, Moreland, JG, Ligeti, E, Nauseef, WM & DeCoursey, TE 2006, 'The antibacterial activity of human neutrophils and eosinophils requires proton channels but not BK channels', Journal of General Physiology, vol. 127, no. 6, pp. 659-672. https://doi.org/10.1085/jgp.200609504
Femling, Jon K. ; Cherny, Vladimir V. ; Morgan, Deri ; Rada, Balázs ; Davis, A. Paige ; Czirják, Gabor ; Enyedi, Peter ; England, Sarah K. ; Moreland, Jessica G. ; Ligeti, Erzsébet ; Nauseef, William M. ; DeCoursey, Thomas E. / The antibacterial activity of human neutrophils and eosinophils requires proton channels but not BK channels. In: Journal of General Physiology. 2006 ; Vol. 127, No. 6. pp. 659-672.
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AU - Femling, Jon K.

AU - Cherny, Vladimir V.

AU - Morgan, Deri

AU - Rada, Balázs

AU - Davis, A. Paige

AU - Czirják, Gabor

AU - Enyedi, Peter

AU - England, Sarah K.

AU - Moreland, Jessica G.

AU - Ligeti, Erzsébet

AU - Nauseef, William M.

AU - DeCoursey, Thomas E.

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N2 - Electrophysiological events are of central importance during the phagocyte respiratory burst, because NADPH oxidase is electrogenic and voltage sensitive. We investigated the recent suggestion that large-conductance, calcium-activated K+ (BK) channels, rather than proton channels, play an essential role in innate immunity (Ahluwalia, J., A. Tinker, L.H. Clapp, M.R. Duchen, A.Y. Abramov, S. Page, M. Nobles, and A.W. Segal. 2004. Nature. 427:853-858). In PMA-stimulated human neutrophils or eosinophils, we did not detect BK currents, and neither of the BK channel inhibitors iberiotoxin or paxilline nor DPI inhibited any component of outward current. BK inhibitors did not inhibit the killing of bacteria, nor did they affect NADPH oxidase-dependent degradation of bacterial phospholipids by extracellular gIIA-PLA2 or the production of superoxide anion (O2.-). Moreover, an antibody against the BK channel did not detect immunoreactive protein in human neutrophils. A required role for voltage-gated proton channels is demonstrated by Zn 2+ inhibition of NADPH oxidase activity assessed by H 2O2 production, thus validating previous studies showing that Zn2+ inhibited O2.- production when assessed by cytochrome c reduction. In conclusion, BK channels were not detected in human neutrophils or eosinophils, and BK inhibitors did not impair antimicrobial activity. In contrast, we present additional evidence that voltage-gated proton channels serve the essential role of charge compensation during the respiratory burst.

AB - Electrophysiological events are of central importance during the phagocyte respiratory burst, because NADPH oxidase is electrogenic and voltage sensitive. We investigated the recent suggestion that large-conductance, calcium-activated K+ (BK) channels, rather than proton channels, play an essential role in innate immunity (Ahluwalia, J., A. Tinker, L.H. Clapp, M.R. Duchen, A.Y. Abramov, S. Page, M. Nobles, and A.W. Segal. 2004. Nature. 427:853-858). In PMA-stimulated human neutrophils or eosinophils, we did not detect BK currents, and neither of the BK channel inhibitors iberiotoxin or paxilline nor DPI inhibited any component of outward current. BK inhibitors did not inhibit the killing of bacteria, nor did they affect NADPH oxidase-dependent degradation of bacterial phospholipids by extracellular gIIA-PLA2 or the production of superoxide anion (O2.-). Moreover, an antibody against the BK channel did not detect immunoreactive protein in human neutrophils. A required role for voltage-gated proton channels is demonstrated by Zn 2+ inhibition of NADPH oxidase activity assessed by H 2O2 production, thus validating previous studies showing that Zn2+ inhibited O2.- production when assessed by cytochrome c reduction. In conclusion, BK channels were not detected in human neutrophils or eosinophils, and BK inhibitors did not impair antimicrobial activity. In contrast, we present additional evidence that voltage-gated proton channels serve the essential role of charge compensation during the respiratory burst.

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