PMID- 10515231
OWN - NLM
STAT- MEDLINE
DCOM- 19991020
LR  - 20190513
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 58
IP  - 10
DP  - 1999 Oct
TI  - Microglial activation by components of gram-positive and -negative bacteria: 
      distinct and common routes to the induction of ion channels and cytokines.
PG  - 1078-89
AB  - Gram-positive Streptococcus pneumoniae is the major pathogen causing lethal 
      meningitis in adults. We used pneumococcal cell walls (PCW) to investigate 
      microglial consequences of a bacterial challenge and to determine the role of 
      serum in the activation process. PCW caused the characteristic induction of an 
      outwardly rectifying K+ channel (IK+(OR)), together with a concomitant 
      suppression of the constitutively expressed inward rectifier K+ current, and 
      evoked the release of tumor necrosis factor-alpha (TNF alpha), interleukin-6 
      (IL-6), IL-12, KC, macrophage inflammatory protein (MIP) 1alpha and MIP-2. Serum 
      presence strongly facilitated the PCW effects, similarly as observed for 
      lipopolysaccharide (LPS) from gram-negative Escherichia coli. The inflammatory 
      cytokine, interferon-gamma (IFNgamma) induced the same electrophysiological 
      changes, but independent of serum. Recombinant LPS binding protein (LBP) could 
      partially replace serum activity in LPS stimulations. In contrast, neither LBP 
      nor an antibody-mediated blockade of the LPS receptor, CD14 had significant 
      influences on PCW-inducible changes. Cell surface interactions and cofactor 
      involvement in microglial activation by gram-positive bacteria are thus distinct 
      from the mechanisms employed by LPS. Moreover, tyrphostin AG126, a protein kinase 
      inhibitor that prevents activation of the mitogen-activated protein kinase, 
      p42MAPK (ERK2), potently blocked the PCW-stimulated cytokine release while having 
      only a limited effect on LPS-inducible cytokines. In contrast, AG126 did not 
      influence IK+(OR) inductions. This indicates that PCW recruits more than 1 
      intracellular signaling pathway to trigger the various responses and that 
      different bacterial agents signal through both common and individual routes 
      during microglial activation.
FAU - Prinz, M
AU  - Prinz M
AD  - Department of Cellular Neurosciences, Max Delbruck Center for Molecular Medicine, 
      Berlin, Germany.
FAU - Kann, O
AU  - Kann O
FAU - Draheim, H J
AU  - Draheim HJ
FAU - Schumann, R R
AU  - Schumann RR
FAU - Kettenmann, H
AU  - Kettenmann H
FAU - Weber, J R
AU  - Weber JR
FAU - Hanisch, U K
AU  - Hanisch UK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Ion Channels)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Potassium Channels)
RN  - 0 (Recombinant Proteins)
RN  - 0 (lipopolysaccharide-binding protein)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - *Acute-Phase Proteins
MH  - Animals
MH  - Animals, Newborn/metabolism
MH  - Blood Physiological Phenomena
MH  - Carrier Proteins/pharmacology
MH  - Cell Wall/physiology
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Drug Synergism
MH  - Embryo, Mammalian/cytology/metabolism
MH  - Gram-Negative Bacteria/*physiology
MH  - Gram-Positive Bacteria/*physiology
MH  - Interferon-gamma/pharmacology
MH  - Ion Channels/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - *Membrane Glycoproteins
MH  - Mice
MH  - Microglia/drug effects/metabolism/*microbiology/*physiology
MH  - Potassium Channels/drug effects/metabolism
MH  - Protein Kinases/physiology
MH  - Recombinant Proteins
MH  - Streptococcus pneumoniae/physiology
EDAT- 1999/10/09 00:00
MHDA- 1999/10/09 00:01
CRDT- 1999/10/09 00:00
PHST- 1999/10/09 00:00 [pubmed]
PHST- 1999/10/09 00:01 [medline]
PHST- 1999/10/09 00:00 [entrez]
AID - 10.1097/00005072-199910000-00006 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 1999 Oct;58(10):1078-89. doi: 
      10.1097/00005072-199910000-00006.