| Title: |
Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils. |
| Authors: |
McNeill, E; Conway, S; Roderick, H; Bootman, MD; Hogg, N |
| Publication Year: |
2016 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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 IP(3) 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 PLCbeta, 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 PLCbeta. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1016/j.ceca.2006.05.004 |
| DOI: |
10.1016/j.ceca.2006.05.004 |
| Availability: |
https://doi.org/10.1016/j.ceca.2006.05.004; https://ora.ox.ac.uk/objects/uuid:9c479a45-5fd1-49f1-9c5f-8e9fe1cae224 |
| Rights: |
info:eu-repo/semantics/embargoedAccess |
| Accession Number: |
edsbas.28522B51 |
| Database: |
BASE |