Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine Neutrophils
The importance of the intracellular Ca2+ concentration ([Ca2+]i) in neutrophil function has been intensely studied. However, the role of the intracellular Na+ concentration ([Na+]i) which is closely linked to the intracellular Ca2+ regulation has been largely overlooked. The [Na+]i is regulated by N...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.02124/full |
| _version_ | 1818381651828277248 |
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| author | Karolina Najder Micol Rugi Micol Rugi Mégane Lebel Julia Schröder Leonie Oster Sandra Schimmelpfennig Sarah Sargin Zoltán Pethő Etmar Bulk Albrecht Schwab |
| author_facet | Karolina Najder Micol Rugi Micol Rugi Mégane Lebel Julia Schröder Leonie Oster Sandra Schimmelpfennig Sarah Sargin Zoltán Pethő Etmar Bulk Albrecht Schwab |
| author_sort | Karolina Najder |
| collection | DOAJ |
| description | The importance of the intracellular Ca2+ concentration ([Ca2+]i) in neutrophil function has been intensely studied. However, the role of the intracellular Na+ concentration ([Na+]i) which is closely linked to the intracellular Ca2+ regulation has been largely overlooked. The [Na+]i is regulated by Na+ transport proteins such as the Na+/Ca2+-exchanger (NCX1), Na+/K+-ATPase, and Na+-permeable, transient receptor potential melastatin 2 (TRPM2) channel. Stimulating with either N-formylmethionine-leucyl-phenylalanine (fMLF) or complement protein C5a causes distinct changes of the [Na+]i. fMLF induces a sustained increase of [Na+]i, surprisingly, reaching higher values in TRPM2−/− neutrophils. This outcome is unexpected and remains unexplained. In both genotypes, C5a elicits only a transient rise of the [Na+]i. The difference in [Na+]i measured at t = 10 min after stimulation is inversely related to neutrophil chemotaxis. Neutrophil chemotaxis is more efficient in C5a than in an fMLF gradient. Moreover, lowering the extracellular Na+ concentration from 140 to 72 mM improves chemotaxis of WT but not of TRPM2−/− neutrophils. Increasing the [Na+]i by inhibiting the Na+/K+-ATPase results in disrupted chemotaxis. This is most likely due to the impact of the altered Na+ homeostasis and presumably NCX1 function whose expression was shown by means of qPCR and which critically relies on proper extra- to intracellular Na+ concentration gradients. Increasing the [Na+]i by a few mmol/l may suffice to switch its transport mode from forward (Ca2+-efflux) to reverse (Ca2+-influx) mode. The role of NCX1 in neutrophil chemotaxis is corroborated by its blocker, which also causes a complete inhibition of chemotaxis. |
| first_indexed | 2024-12-14T02:37:58Z |
| format | Article |
| id | doaj.art-0a3792d0f6b749b495e64f3695b5c8ac |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T02:37:58Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0a3792d0f6b749b495e64f3695b5c8ac2022-12-21T23:20:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.02124530647Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine NeutrophilsKarolina Najder0Micol Rugi1Micol Rugi2Mégane Lebel3Julia Schröder4Leonie Oster5Sandra Schimmelpfennig6Sarah Sargin7Zoltán Pethő8Etmar Bulk9Albrecht Schwab10Institute of Physiology II, University Hospital Münster, Münster, GermanyInstitute of Physiology II, University Hospital Münster, Münster, GermanyUniversity of Florence, Florence, ItalyUniversity of Sherbrooke, Sherbrooke, QC, CanadaInstitute of Physiology II, University Hospital Münster, Münster, GermanyInstitute of Physiology II, University Hospital Münster, Münster, GermanyInstitute of Physiology II, University Hospital Münster, Münster, GermanyInstitute of Physiology II, University Hospital Münster, Münster, GermanyInstitute of Physiology II, University Hospital Münster, Münster, GermanyInstitute of Physiology II, University Hospital Münster, Münster, GermanyInstitute of Physiology II, University Hospital Münster, Münster, GermanyThe importance of the intracellular Ca2+ concentration ([Ca2+]i) in neutrophil function has been intensely studied. However, the role of the intracellular Na+ concentration ([Na+]i) which is closely linked to the intracellular Ca2+ regulation has been largely overlooked. The [Na+]i is regulated by Na+ transport proteins such as the Na+/Ca2+-exchanger (NCX1), Na+/K+-ATPase, and Na+-permeable, transient receptor potential melastatin 2 (TRPM2) channel. Stimulating with either N-formylmethionine-leucyl-phenylalanine (fMLF) or complement protein C5a causes distinct changes of the [Na+]i. fMLF induces a sustained increase of [Na+]i, surprisingly, reaching higher values in TRPM2−/− neutrophils. This outcome is unexpected and remains unexplained. In both genotypes, C5a elicits only a transient rise of the [Na+]i. The difference in [Na+]i measured at t = 10 min after stimulation is inversely related to neutrophil chemotaxis. Neutrophil chemotaxis is more efficient in C5a than in an fMLF gradient. Moreover, lowering the extracellular Na+ concentration from 140 to 72 mM improves chemotaxis of WT but not of TRPM2−/− neutrophils. Increasing the [Na+]i by inhibiting the Na+/K+-ATPase results in disrupted chemotaxis. This is most likely due to the impact of the altered Na+ homeostasis and presumably NCX1 function whose expression was shown by means of qPCR and which critically relies on proper extra- to intracellular Na+ concentration gradients. Increasing the [Na+]i by a few mmol/l may suffice to switch its transport mode from forward (Ca2+-efflux) to reverse (Ca2+-influx) mode. The role of NCX1 in neutrophil chemotaxis is corroborated by its blocker, which also causes a complete inhibition of chemotaxis.https://www.frontiersin.org/article/10.3389/fimmu.2020.02124/fullneutrophilchemotaxisintracellular sodiumNCX1TRP channels |
| spellingShingle | Karolina Najder Micol Rugi Micol Rugi Mégane Lebel Julia Schröder Leonie Oster Sandra Schimmelpfennig Sarah Sargin Zoltán Pethő Etmar Bulk Albrecht Schwab Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine Neutrophils Frontiers in Immunology neutrophil chemotaxis intracellular sodium NCX1 TRP channels |
| title | Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine Neutrophils |
| title_full | Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine Neutrophils |
| title_fullStr | Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine Neutrophils |
| title_full_unstemmed | Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine Neutrophils |
| title_short | Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine Neutrophils |
| title_sort | role of the intracellular sodium homeostasis in chemotaxis of activated murine neutrophils |
| topic | neutrophil chemotaxis intracellular sodium NCX1 TRP channels |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.02124/full |
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