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| Item Type: | Article |
|---|---|
| Title: | 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 |
| Creators Name: | Hoffmann, A. and Kann, O. and Ohlemeyer, C. and Hanisch, U.K. and Kettenmann, H. |
| 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. |
| Keywords: | BAPTA, C5a, CD88, Fura-2, Ionomycin, UTP, Animals, Mice |
| Source: | Journal of Neuroscience |
| ISSN: | 0270-6474 |
| Publisher: | Society for Neuroscience |
| Volume: | 23 |
| Number: | 11 |
| Page Range: | 4410-4419 |
| Date: | 1 June 2003 |
| Additional Information: | Copyright (c) 2003 by The Society for Neuroscience |
| Official Publication: | http://www.jneurosci.org/cgi/content/abstract/23/11/4410 |
| PubMed: | View item in PubMed |
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