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BK channels in innate immune functions of neutrophils and macrophages
- Publication Year :
- 2009
- Publisher :
- American Society of Hematology, 2009.
-
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-α 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-κB 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-α release and signal transduction BMDMs.
- Subjects :
- Lipopolysaccharides
Male
BK channel
Indoles
Neutrophils
Immunology
Biology
Biochemistry
p38 Mitogen-Activated Protein Kinases
Muscle, Smooth, Vascular
chemistry.chemical_compound
Phagocytes, Granulocytes, and Myelopoiesis
Mice
Phosphatidylinositol 3-Kinases
Superoxides
Macrophage
Animals
Large-Conductance Calcium-Activated Potassium Channels
Respiratory Burst
Mice, Knockout
Mitogen-Activated Protein Kinase 1
Oxidase test
Phagocytes
NADPH oxidase
Mitogen-Activated Protein Kinase 3
Superoxide
Tumor Necrosis Factor-alpha
Macrophages
NF-kappa B
NADPH Oxidases
Cell Biology
Hematology
Flow Cytometry
Immunity, Innate
Respiratory burst
Cell biology
Mice, Inbred C57BL
Tibial Arteries
chemistry
biology.protein
Tumor necrosis factor alpha
Female
Proto-Oncogene Proteins c-akt
Nicotinamide adenine dinucleotide phosphate
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....addf7c86cc0ae118d348e43eccee2083