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2003. Elevation of basal intracellular calcium as a central element in the activation of brain macrophages (microglia): suppression of receptor-evoked calcium signaling and control of release function
| Venue: | J. Neurosci |
| Citations: | 5 - 0 self |
BibTeX
@ARTICLE{Hoffmann_2003.elevation,
author = {Anja Hoffmann and Oliver Kann and Carsten Ohlemeyer and Uwe-karsten Hanisch and Helmut Kettenmann},
title = {2003. Elevation of basal intracellular calcium as a central element in the activation of brain macrophages (microglia): suppression of receptor-evoked calcium signaling and control of release function},
journal = {J. Neurosci},
year = {},
pages = {4410--4419}
}
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Abstract
Microglia – brain macrophages are immune-competent cells of the CNS and respond to pathologic events. Using bacterial lipopolysaccharide (LPS) as a tool to activate cultured mouse microglia, we studied alterations in the intracellular calcium concentration ([Ca 2 � ] i) and in the receptor-evoked generation of transient calcium signals. LPS treatment led to a chronic elevation of basal [Ca 2 � ] i along with a suppression of evoked calcium signaling, as indicated by reduced [Ca 2 � ] i transients during stimulation with UTP and complement factor 5a. Presence of the calcium chelator BAPTA prevented the activation-associated changes in [Ca 2 � ] i and restored much of the signaling efficacy. We also evaluated downstream consequences of a basal [Ca 2 � ] i lifting during microglial activation and found BAPTA to strongly attenuate the LPS-induced release of nitric oxide (NO) and certain cytokines and chemokines. Furthermore, microglial treatment with ionomycin, an ionophore elevating basal [Ca 2 � ] i, mimicked the activation-induced calcium signal suppression but failed to induce release activity on its own. Our findings suggest that chronic elevation of basal [Ca 2 � ] i attenuates receptor-triggered calcium signaling. Moreover, increased [Ca 2 � ] i is required, but by itself is not sufficient, for release of NO and certain cytokines and chemokines. Elevation of basal [Ca 2 � ] i could thus prove a central element in the regulation of executive functions in activated microglia.
Keyphrases
basal ca central element release function brain macrophage basal intracellular calcium receptor-evoked calcium chronic elevation certain cytokine bacterial lipopolysaccharide mouse microglia lps-induced release complement factor release activity immune-competent cell microglia brain macrophage microglial treatment activation-induced calcium signal suppression activated microglia reduced ca lp treatment executive function receptor-evoked generation activation-associated change nitric oxide transient calcium signal intracellular calcium concentration microglial activation downstream consequence calcium chelator bapta evoked calcium signaling receptor-triggered calcium signaling
