The Journal of General Physiology
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Published online 15 May 2006 doi:10.1085/jgp.200609504
The Rockefeller University Press, 0022-1295 $8.00
JGP, Volume 127, Number 6, 659-672
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ARTICLE

 The Antibacterial Activity of Human Neutrophils and Eosinophils Requires Proton Channels but Not BK Channels



Jon K. Femling2,4, Vladimir V. Cherny1, Deri Morgan1, Balázs Rada7, A. Paige Davis2,6, Gabor Czirják7, Peter Enyedi7, Sarah K. England5, Jessica G. Moreland2,6, Erzsébet Ligeti7, William M. Nauseef2,3,4, and Thomas E. DeCoursey1

1 Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL 60612
2 Inflammation Program, 3 Department of Medicine, 4 Department of Microbiology, 5 Department of Physiology and Biophysics, and 6 Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Coralville, IA 52241
7 Department of Physiology, Semmelweis University, H-1444 Budapest 8, Hungary

Correspondence to Thomas E. DeCoursey: tdecours{at}rush.edu

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 (Formula). 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 Zn2+ inhibition of NADPH oxidase activity assessed by H2O2 production, thus validating previous studies showing that Zn2+ inhibited Formula 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.

Abbreviations used in this paper: BK channel, large-conductance, calcium-activated, potassium-selective channel; CCCP, carbonyl cyanide m-chlorophenylhydrazone; DPI, diphenylene iodonium; HRP, horseradish peroxidase; IbTX, iberiotoxin; IK, intermediate-conductance Ca2+-activated K+; KMeSO3, potassium methanesulfonate; PAX, paxilline; PMN, polymorphonuclear leukocytes.


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