A macrophage cell model for pH and volume regulation

Luo, Chi‐Cheng; Clark, Jr Jw; Heming, T.A.; Bidani, A.

doi:10.1016/j.jtbi.2005.06.002

Cited by 3 publications

(2 citation statements)

References 17 publications

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“…The proton pump was suggested to participate in volume regulation in microglia, macrophages, and T lymphocytes (538). Proton pump inhibitors possess anti-inflammatory effects and can decrease human microglial and monocytic neurotoxicity.…”

Section: Proton Pumpmentioning

confidence: 99%

Physiology of Microglia

Kettenmann

Hanisch

Нода

et al. 2011

Physiological Reviews

3,134

2,981

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Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed “resting microglia.” Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the “activated microglial cell.” This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

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Section: Proton Pumpmentioning

confidence: 99%

Physiology of Microglia

Kettenmann

Hanisch

Нода

et al. 2011

Physiological Reviews

3,134

2,981

View full text Add to dashboard Cite

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“…Inside the cells, protonation of NH 3 determines an increase in pH i that will proceed until NH 3 achieves equilibrium across the plasma membrane. During this process, NH 4 + is generated and can be accumulated intracellularly in millimolar concentrations [11,19,20]. Thus, a net intracellular accumulation of osmotically active particles (NH 4 + ) proceeds concomitantly with the change in pH i .…”

Section: Introductionmentioning

confidence: 99%

Parallel Changes in Intracellular Water Volume and pH Induced by NH₃/NH₄⁺Exposure in Single Neuroblastoma Cells

Blanco

Márquez

Álvarez-Leefmans

2013

Cell Physiol Biochem

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Background: Increased blood levels of ammonia (NH₃) and ammonium (NH₄⁺), i.e. hyperammonemia, leads to cellular brain edema in humans with acute liver failure. The pathophysiology of this edema is poorly understood. This is partly due to incomplete understanding of the osmotic effects of the pair NH₃/NH₄⁺ at the cellular and molecular levels. Cell exposure to solutions containing NH₃/NH₄⁺ elicits changes in intracellular pH (pH_i), which can in turn affect cell water volume (CWV) by activating transport mechanisms that produce net gain or loss of solutes and water. The occurrence of CWV changes caused by NH₃/NH₄⁺ has long been suspected, but the mechanisms, magnitude and kinetics of these changes remain unknown. Methods: Using fluorescence imaging microscopy we measured, in real time, parallel changes in pH_i and CWV caused by brief exposure to NH₃/NH₄⁺ of single cells (N1E-115 neuroblastoma or NG-108 neuroblastoma X glioma ) loaded with the fluorescent indicator BCECF. Changes in CWV were measured by exciting BCECF at its intracellular isosbestic wavelength (∼438 nm), and pH_i was measured ratiometrically. Results: Brief exposure to isosmotic solutions (i.e. having the same osmolality as that of control solutions) containing NH₄Cl (0.5- 30 mM) resulted in a rapid, dose-dependent swelling, followed by isosmotic regulatory volume decrease (iRVD). NH₄Cl solutions in which either extracellular [NH₃] or [NH₄⁺] was kept constant while the other was changed by varying the pH of the solution, demonstrated that [NH₃]_o rather than [NH₄⁺]_o is the main determinant of the NH₄Cl-induced swelling. The iRVD response was sensitive to the anion channel blocker NPPB, and partly dependent on external Ca²⁺. Upon removal of NH₄Cl, cells shrank and displayed isosmotic regulatory volume increase (iRVI). Regulatory volume responses could not be activated by comparable CWV changes produced by anisosmotic solutions, suggesting that membrane stretch or contraction by themselves are not sufficient to trigger these responses. Inhibition of glutamine synthetase partially blocked the NH₄Cl-induced swelling. Conclusions: A quantitative description of the osmotic changes produced by exposure to NH₃/NH₄⁺ in single neurons and glial cells shows that ∼35 to 45% of the initial cell swelling can be explained by intracellular accumulation of NH₄⁺ due to rapid permeation and protonation of NH₃. Another∼23% of the swelling can be accounted for by rapid glutamine accumulation. The results are discussed in terms of basic cell physiology and their potential relevance to the pathophysiology of hyperammonemic cellular brain edema.

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“Herstory” versus “history”: A motherist rememory in Akachi Ezeigbo’s The Last of the Strong Ones and Chimamanda Adichie’s Half of a Yellow Sun

Etim

2020

Cogent Arts & Humanities

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A macrophage cell model for pH and volume regulation

Cited by 3 publications

References 17 publications

Physiology of Microglia

Physiology of Microglia

Parallel Changes in Intracellular Water Volume and pH Induced by NH₃/NH₄⁺Exposure in Single Neuroblastoma Cells

“Herstory” versus “history”: A motherist rememory in Akachi Ezeigbo’s The Last of the Strong Ones and Chimamanda Adichie’s Half of a Yellow Sun

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A macrophage cell model for pH and volume regulation

Cited by 3 publications

References 17 publications

Physiology of Microglia

Physiology of Microglia

Parallel Changes in Intracellular Water Volume and pH Induced by NH3/NH4+Exposure in Single Neuroblastoma Cells

“Herstory” versus “history”: A motherist rememory in Akachi Ezeigbo’s The Last of the Strong Ones and Chimamanda Adichie’s Half of a Yellow Sun

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Parallel Changes in Intracellular Water Volume and pH Induced by NH₃/NH₄⁺Exposure in Single Neuroblastoma Cells