Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils

E. McNeill, S. J. Conway, H. L. Roderick, M. D. Bootman, N. Hogg

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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 languageEnglish
Pages (from-to)107-121
Number of pages15
JournalCell Calcium
Volume41
DOIs
Publication statusPublished - 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

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