Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils.
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 c...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2007
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| _version_ | 1797084624793370624 |
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| author | McNeill, E Conway, S Roderick, H Bootman, MD Hogg, N |
| author_facet | McNeill, E Conway, S Roderick, H Bootman, MD Hogg, N |
| author_sort | McNeill, E |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T01:57:42Z |
| format | Journal article |
| id | oxford-uuid:9c479a45-5fd1-49f1-9c5f-8e9fe1cae224 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:57:42Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:9c479a45-5fd1-49f1-9c5f-8e9fe1cae2242022-03-27T00:34:55ZDefective chemoattractant-induced calcium signalling in S100A9 null neutrophils.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9c479a45-5fd1-49f1-9c5f-8e9fe1cae224EnglishSymplectic Elements at Oxford2007McNeill, EConway, SRoderick, HBootman, MDHogg, NThe 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. |
| spellingShingle | McNeill, E Conway, S Roderick, H Bootman, MD Hogg, N Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils. |
| title | Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils. |
| title_full | Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils. |
| title_fullStr | Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils. |
| title_full_unstemmed | Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils. |
| title_short | Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils. |
| title_sort | defective chemoattractant induced calcium signalling in s100a9 null neutrophils |
| work_keys_str_mv | AT mcneille defectivechemoattractantinducedcalciumsignallingins100a9nullneutrophils AT conways defectivechemoattractantinducedcalciumsignallingins100a9nullneutrophils AT roderickh defectivechemoattractantinducedcalciumsignallingins100a9nullneutrophils AT bootmanmd defectivechemoattractantinducedcalciumsignallingins100a9nullneutrophils AT hoggn defectivechemoattractantinducedcalciumsignallingins100a9nullneutrophils |