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

被引:8
作者
Najder, Karolina [1 ]
Rugi, Micol [1 ,2 ]
Lebel, Megane [3 ]
Schroeder, Julia [1 ]
Oster, Leonie [1 ]
Schimmelpfennig, Sandra [1 ]
Sargin, Sarah [1 ]
Petho, Zoltan [1 ]
Bulk, Etmar [1 ]
Schwab, Albrecht [1 ]
机构
[1] Univ Hosp Munster, Inst Physiol 2, Munster, Germany
[2] Univ Florence, Florence, Italy
[3] Univ Sherbrooke, Sherbrooke, PQ, Canada
来源
FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷
基金
欧盟地平线“2020”;
关键词
neutrophil; chemotaxis; intracellular sodium; NCX1; TRP channels; NADPH OXIDASE; CALCIUM EXCHANGE; OXIDATIVE STRESS; ADP-RIBOSE; G-PROTEINS; TRPM2; MEMBRANE; CA2+; NA+/H+; GRANULOCYTES;
D O I
10.3389/fimmu.2020.02124
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The importance of the intracellular Ca(2+)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 Ca(2+)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 att= 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.
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页数:15
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