BK Channels in Innate Immune Functions of Neutrophils and Macrophages

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2008 Dec 17

PMID 19074007

Citations 25

Authors

Kirill Essin

Maik Gollasch

Susanne Rolle

Patrick Weissgerber

Matthias Sausbier

Erwin Bohn

Ingo B Autenrieth

Peter Ruth

Friedrich C Luft

William M Nauseef

Ralph Kettritz

Affiliations

Soon will be listed here.

Abstract

Oxygen-dependent antimicrobial activity of human polymorphonuclear leukocytes (PMNs) relies on the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate oxidants. As the oxidase transfers electrons from NADPH the membrane will depolarize and concomitantly terminate oxidase activity, unless there is charge translocation to compensate. Most experimental data implicate proton channels as the effectors of this charge compensation, although large-conductance Ca2+-activated K+ (BK) channels have been suggested to be essential for normal PMN antimicrobial activity. To test this latter notion, we directly assessed the role of BK channels in phagocyte function, including the NADPH oxidase. PMNs genetically lacking BK channels (BK(-/-)) had normal intracellular and extracellular NADPH oxidase activity in response to both receptor-independent and phagocytic challenges. Furthermore, NADPH oxidase activity of human PMNs and macrophages was normal after treatment with BK channel inhibitors. Although BK channel inhibitors suppressed endotoxin-mediated tumor necrosis factor-alpha secretion by bone marrow-derived macrophages (BMDMs), BMDMs of BK(-/-) and wild-type mice responded identically and exhibited the same ERK, PI3K/Akt, and nuclear factor-kappaB activation. Based on these data, we conclude that the BK channel is not required for NADPH oxidase activity in PMNs or macrophages or for endotoxin-triggered tumor necrosis factor-alpha release and signal transduction BMDMs.

Citing Articles

The BK Channel Limits the Pro-Inflammatory Activity of Macrophages.

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Nonmyocytes as electrophysiological contributors to cardiac excitation and conduction.

Simon-Chica A, Wulfers E, Kohl P Am J Physiol Heart Circ Physiol. 2023; 325(3):H475-H491.

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BK Channels Regulate LPS-induced CCL-2 Release from Human Pulmonary Endothelial Cells.

Zyrianova T, Lopez B, Liao A, Gu C, Wong L, Ottolia M Am J Respir Cell Mol Biol. 2020; 64(2):224-234.

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-linked channelopathy.

Bailey C, Moldenhauer H, Park S, Keros S, Meredith A J Gen Physiol. 2019; 151(10):1173-1189.

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The intimate and controversial relationship between voltage-gated proton channels and the phagocyte NADPH oxidase.

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