PMID- 20857304
OWN - NLM
STAT- MEDLINE
DCOM- 20110203
LR  - 20211020
IS  - 1432-2013 (Electronic)
IS  - 0031-6768 (Linking)
VI  - 460
IP  - 6
DP  - 2010 Nov
TI  - Phosphoinositide 3-kinase-dependent regulation of Na+/H+ exchanger in dendritic 
      cells.
PG  - 1087-96
LID - 10.1007/s00424-010-0879-0 [doi]
AB  - Dendritic cells (DCs), antigen-presenting cells that are able to initiate primary 
      immune responses and to establish immunological memory, are activated by exposure 
      to bacterial lipopolysaccharides (LPS), which leads to cell swelling, triggering 
      ROS formation and stimulating migration. The function of DCs is regulated by the 
      phosphoinositide 3 (PI3) kinase pathway. On the other hand, PI3 kinase is an 
      important regulator of diverse transporters including the Na(+)/H(+) exchanger 
      (NHE). The present study was performed to elucidate the role of PI3 kinase in NHE 
      activity, cell volume, ROS formation, and migration. To this end, DCs were 
      isolated from murine bone marrow, cytosolic pH (pH(i)) determined utilizing 
      2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein fluorescence, Na(+)/H(+) 
      exchanger activity from the Na(+)-dependent realkalinization after an ammonium 
      pulse, cell volume from forward scatter in fluorescence-activated cell sorter 
      analysis, ROS production from 2',7'-dichlorodihydrofluorescein diacetate 
      fluorescence, and migration utilizing transwell migration assays. Exposure of DCs 
      to LPS led within 4 h to a gradual cytosolic acidification paralleled by a 
      transient time- and dose-dependent increase of Na(+)/H(+) exchanger activity, 
      cell swelling, enhanced ROS production, and stimulation of migration. The PI3K 
      inhibitors Wortmannin (1 muM) or LY294002 (10 muM) significantly blunted the 
      effects of LPS on NHE activity, cell volume, ROS production, and migration. The 
      present observations disclose a critical role of PI3K signaling in the regulation 
      of DC function following exposure to LPS.
FAU - Rotte, Anand
AU  - Rotte A
AD  - Department of Physiology, University of Tubingen, 72076 Tubingen, Germany.
FAU - Pasham, Venkanna
AU  - Pasham V
FAU - Yang, Wenting
AU  - Yang W
FAU - Eichenmuller, Melanie
AU  - Eichenmuller M
FAU - Bhandaru, Madhuri
AU  - Bhandaru M
FAU - Shumilina, Ekaterina
AU  - Shumilina E
FAU - Lang, Florian
AU  - Lang F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100921
PL  - Germany
TA  - Pflugers Arch
JT  - Pflugers Archiv : European journal of physiology
JID - 0154720
RN  - 0 (Androstadienes)
RN  - 0 (Chromones)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Cell Size
MH  - Cells, Cultured
MH  - Chromones/pharmacology
MH  - Dendritic Cells/drug effects/*metabolism
MH  - Female
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Morpholines/pharmacology
MH  - Phosphatidylinositol 3-Kinase/*physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Sodium-Hydrogen Exchangers/*metabolism
MH  - Wortmannin
EDAT- 2010/09/22 06:00
MHDA- 2011/02/04 06:00
CRDT- 2010/09/22 06:00
PHST- 2010/05/25 00:00 [received]
PHST- 2010/09/01 00:00 [accepted]
PHST- 2010/07/14 00:00 [revised]
PHST- 2010/09/22 06:00 [entrez]
PHST- 2010/09/22 06:00 [pubmed]
PHST- 2011/02/04 06:00 [medline]
AID - 10.1007/s00424-010-0879-0 [doi]
PST - ppublish
SO  - Pflugers Arch. 2010 Nov;460(6):1087-96. doi: 10.1007/s00424-010-0879-0. Epub 2010 
      Sep 21.