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Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils

McNeill, E.; Conway, S. J.; Roderick, H. L.; Bootman, M. D. and Hogg, N. (2007). Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils. Cell Calcium, 41(2) pp. 107–121.

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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
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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