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 S 100A9 null neutrophils was less susceptible than wildtype to PLC beta inhibition, revealing dis-regulation of the signalling pathway at this level. Downstream of PLC beta, 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 PLC beta. (c) 2006 Elsevier Ltd. All rights reserved.
Original language | English |
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Pages (from-to) | 107-121 |
Number of pages | 15 |
Journal | Cell Calcium |
Volume | 41 |
DOIs | |
Publication status | Published - Feb 2007 |
Keywords
- S100
- knockout
- neutrophil
- chemokine
- calcium
- EF-HAND PROTEINS
- PHOSPHOLIPASE-C
- ENDOTHELIAL-CELLS
- INSP(3) RECEPTOR
- PLASMA-MEMBRANE
- MRP14
- FAMILY
- MICE
- MONOCYTES
- MRP-14