Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine Neutrophils.

Autor:	Najder K; Institute of Physiology II, University Hospital Münster, Münster, Germany., Rugi M; Institute of Physiology II, University Hospital Münster, Münster, Germany.; University of Florence, Florence, Italy., Lebel M; University of Sherbrooke, Sherbrooke, QC, Canada., Schröder J; Institute of Physiology II, University Hospital Münster, Münster, Germany., Oster L; Institute of Physiology II, University Hospital Münster, Münster, Germany., Schimmelpfennig S; Institute of Physiology II, University Hospital Münster, Münster, Germany., Sargin S; Institute of Physiology II, University Hospital Münster, Münster, Germany., Pethő Z; Institute of Physiology II, University Hospital Münster, Münster, Germany., Bulk E; Institute of Physiology II, University Hospital Münster, Münster, Germany., Schwab A; Institute of Physiology II, University Hospital Münster, Münster, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Sep 08; Vol. 11, pp. 2124. Date of Electronic Publication: 2020 Sep 08 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.02124
Abstrakt:	The importance of the intracellular Ca ²⁺ concentration ([Ca ²⁺ ] 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 Ca ²⁺ regulation has been largely overlooked. The [Na ⁺ ] i is regulated by Na ⁺ transport proteins such as the Na ⁺ /Ca ²⁺ -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 (Ca ²⁺ -efflux) to reverse (Ca ²⁺ -influx) mode. The role of NCX1 in neutrophil chemotaxis is corroborated by its blocker, which also causes a complete inhibition of chemotaxis. (Copyright © 2020 Najder, Rugi, Lebel, Schröder, Oster, Schimmelpfennig, Sargin, Pethő, Bulk and Schwab.)
Databáze:	MEDLINE
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