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The Role of Na+/H+ Exchanger Isoform 1 in Inflammatory Responses: Maintaining H+ Homeostasis of Immune Cells

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Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 961))

Abstract

The Na+/H+ exchangers (NHEs) are a family of membrane transporter proteins which catalyze the electroneutral exchange of one Na+ for one H+ and thus regulate intracellular pH (pHi) and cell volume. It is shown that Na+/H+ exchanger isoform 1 (NHE-1), but not other isoforms, is the important mechanism in extruding H+ and regulating pHi in the immune system. Immune cells, such as monocytes and neutrophils, generate reactive oxygen species (ROS) and cytokines in response to various stimuli and provide the first line of defense in the immune system. NHE-1 is activated during this respiratory burst and required to maintain an optimal pHi for the immune cells. In the central nervous system, NHE-1 is important for microglial (macrophage) activation and participates in the inflammatory response under pathological conditions including cerebral ischemia and traumatic brain injury. NHE-1 also affects Ca2+ homeostasis in microglia and contributes to the increase of [Ca2+]i by coupling to the Na+/Ca2+ exchanger (NCX) stimulation, thus regulating immune cell function and participating in ischemic cell death. A better understanding of the function of NHE-1 in inflammatory responses will provide insight into its role in brain damage under disease conditions.

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Acknowledgments

This work was supported by NIH grants R01NS 48216 and R01NS 38118 (D. Sun). We would like to thank Douglas B. Kintner for his critical comments of the manuscript.

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Authors and Affiliations

  1. Department of Neurology, University of Pittsburgh Medical School, S-598 South Biomedical Science Tower (BST), 3500 Terrace Street, Pittsburgh, PA, 15213, USA

    Yejie Shi, Dong Kim, Marie Caldwell & Dandan Sun M.D., Ph.D.

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  1. Yejie Shi
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  4. Dandan Sun M.D., Ph.D.
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Correspondence to Dandan Sun M.D., Ph.D. .

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  1. Dipto. Neuroscienze e di, Università di Napoli Fac. Medicina e Chirurgia, Napoli, Italy

    Lucio Annunziato

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Shi, Y., Kim, D., Caldwell, M., Sun, D. (2013). The Role of Na+/H+ Exchanger Isoform 1 in Inflammatory Responses: Maintaining H+ Homeostasis of Immune Cells. In: Annunziato, L. (eds) Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications. Advances in Experimental Medicine and Biology, vol 961. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4756-6_35

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