PMID- 19074007
OWN - NLM
STAT- MEDLINE
DCOM- 20090226
LR  - 20211020
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 113
IP  - 6
DP  - 2009 Feb 5
TI  - BK channels in innate immune functions of neutrophils and macrophages.
PG  - 1326-31
LID - 10.1182/blood-2008-07-166660 [doi]
AB  - 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.
FAU - Essin, Kirill
AU  - Essin K
AD  - Department of Nephrology, Campus-Virchow, Medical Faculty of the Charite, 
      Experimental and Clinical Research Center at the Max Delbruck Center for 
      Molecular Medicine, Berlin, Germany.
FAU - Gollasch, Maik
AU  - Gollasch M
FAU - Rolle, Susanne
AU  - Rolle S
FAU - Weissgerber, Patrick
AU  - Weissgerber P
FAU - Sausbier, Matthias
AU  - Sausbier M
FAU - Bohn, Erwin
AU  - Bohn E
FAU - Autenrieth, Ingo B
AU  - Autenrieth IB
FAU - Ruth, Peter
AU  - Ruth P
FAU - Luft, Friedrich C
AU  - Luft FC
FAU - Nauseef, William M
AU  - Nauseef WM
FAU - Kettritz, Ralph
AU  - Kettritz R
LA  - eng
GR  - R56 AI034879/AI/NIAID NIH HHS/United States
GR  - I01 BX000513/BX/BLRD VA/United States
GR  - AI 34879-19/AI/NIAID NIH HHS/United States
GR  - R01 AI034879/AI/NIAID NIH HHS/United States
GR  - AI 070958/AI/NIAID NIH HHS/United States
GR  - R56 AI070958/AI/NIAID NIH HHS/United States
GR  - R01 AI070958/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20081210
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Indoles)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11062-77-4 (Superoxides)
RN  - 3T9U9Z96L7 (paxilline)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Female
MH  - Flow Cytometry
MH  - *Immunity, Innate
MH  - Indoles/pharmacology
MH  - Large-Conductance Calcium-Activated Potassium Channels/*physiology
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Muscle, Smooth, Vascular/cytology/metabolism
MH  - NADPH Oxidases/metabolism
MH  - NF-kappa B/metabolism
MH  - Neutrophils/*immunology
MH  - Phagocytes/physiology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Respiratory Burst
MH  - Signal Transduction
MH  - Superoxides/metabolism
MH  - Tibial Arteries/cytology/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC2637195
EDAT- 2008/12/17 09:00
MHDA- 2009/02/27 09:00
PMCR- 2010/02/05
CRDT- 2008/12/17 09:00
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/02/27 09:00 [medline]
PHST- 2010/02/05 00:00 [pmc-release]
AID - S0006-4971(20)37756-9 [pii]
AID - 2008/166660 [pii]
AID - 10.1182/blood-2008-07-166660 [doi]
PST - ppublish
SO  - Blood. 2009 Feb 5;113(6):1326-31. doi: 10.1182/blood-2008-07-166660. Epub 2008 
      Dec 10.