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.

DOI: https://doi.org/10.1016/j.ceca.2006.05.004

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.

Viewing alternatives

Metrics

Item Actions

Export

You can export this page using these formats Digital Object Identifier - DOI