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Published on: June 8, 2012
Na(+)-H+ exchange in resident alveolar macrophages: activation by osmotic cell shrinkage
1Department of Internal Medicine & Physiology, University of Texas Medical Branch, Galveston 77555-0561, USA.
Abstract:
Intracellular pH (pHi) homeostasis in resident alveolar macrophages (m phi) under nominally CO2-free conditions is mediated primarily by the activity of plasmalemmal H(+)-ATPase. The m phi also possess an Na(+)-H+ exchanger (NHE) but this mechanism has no detectable role in pHi regulation in the physiologic range. To further explore the physiological significance of the NHE in this cell type, resident alveolar m phi from rabbits were subjected to a hyperosmotic challenge (approximately 620 mOsm/kg) in the nominal absence of CO2-HCO3-. Osmotic cell shrinkage was accompanied by an amiloride-sensitive increase in baseline pHi. The NHE-mediated rate of pHi recovery from intracellular acid loads also increased under hyperosmotic conditions. Cell shrinkage caused an alkaline shift in the pHi set point of the NHE without altering the exchanger's affinity for extracellular Na+. The results indicate that Na(+)-H+ exchange in resident alveolar m phi is activated by osmotic cell shrinkage and imply that the NHE may be involved in volume regulatory responses of the cell.
Insights
Resident alveolar macrophages use the sodium-hydrogen exchanger (NHE) to regulate intracellular pH (pHi) during osmotic cell shrinkage. This finding suggests the NHE plays a role in the cell volume regulatory response.
Area of Science:
- Cellular Physiology
- Macrophage Biology
- Ion Transport
Background:
- Intracellular pH (pHi) homeostasis in alveolar macrophages is mainly regulated by H(+)-ATPase.
- The Na(+)-H+ exchanger (NHE) has a limited role in pHi regulation under physiological conditions.
Purpose of the Study:
- To investigate the physiological significance of the NHE in resident alveolar macrophages.
- To determine the role of NHE in pHi regulation under hyperosmotic conditions.
Main Methods:
- Resident rabbit alveolar macrophages were subjected to hyperosmotic challenges.
- Intracellular pH (pHi) and Na(+)-H+ exchanger activity were measured.
- Amiloride sensitivity was assessed.
Main Results:
- Hyperosmotic stress induced cell shrinkage and an amiloride-sensitive increase in baseline pHi.
- NHE-mediated pHi recovery from acid loads was enhanced under hyperosmotic conditions.
- Cell shrinkage shifted the NHE's pHi set point without affecting extracellular Na+ affinity.
Conclusions:
- Na(+)-H+ exchange in alveolar macrophages is activated by osmotic cell shrinkage.
- The NHE may be involved in the volume regulatory response of these cells.
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