McNeill, E.; Conway, S. J.; Roderick, H. L.; Bootman, M. D. and Hogg, N.
(2007).
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| DOI (Digital Object Identifier) Link: | http://dx.doi.org/10.1016/j.ceca.2006.05.004 |
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Abstract
The S100 family member S100A9 and its heterodimeric partner, S100A8, are cytosolic Ca2+ binding proteins abundantly expressed in neutrophils. To understand the role of this EF-hand-containing complex in Ca2+ signalling, neutrophils from S100A9 null mice were investigated. There was no role for the complex in buffering acute cytosolic Ca2+ elevations. However, Ca2+ responses to inflammatory agents such as chemokines MIP-2 and KC and other agonists are altered. For S100A9 null neutrophils, signalling at the level of G proteins is normal, as is release of Ca2+ from the IP3 receptor-gated intracellular stores. However MIP-2 and FMLP signalling in S100A9 null neutrophils was less susceptible than wildtype to PLCbeta inhibition, revealing dis-regulation of the signalling pathway at this level. Downstream of PLCβ, there was reduced intracellular Ca2+ release induced by sub-maximal levels of chemokines. Conversely the response to FMLP was uncompromised, demonstrating different regulation compared to MIP-2 stimulation. Study of the activity of PLC product DAG revealed that chemokine-induced signalling was susceptible to inhibition by elevated DAG with S100A9 null cells showing enhanced inhibition by DAG. This study defines a lesion in S100A9 null neutrophils associated with inflammatory agonist-induced IP3-mediated Ca2+ release that is manifested at the level of PLCβ.
| Item Type: | Journal Article |
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| Copyright Holders: | 2006 Elsevier Ltd. |
| ISSN: | 1532-1991 |
| Keywords: | S100; knockout; neutrophil; chemokine; calcium |
| Academic Unit/Department: | Science > Life, Health and Chemical Sciences |
| Interdisciplinary Research Centre: | Biomedical Research Network (BRN) |
| Item ID: | 34879 |
| Depositing User: | Martin Bootman |
| Date Deposited: | 25 Oct 2012 09:57 |
| Last Modified: | 21 Mar 2014 09:04 |
| URI: | http://oro.open.ac.uk/id/eprint/34879 |
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