Intracellular LPS inhibits the activity of potassium channels and fails to activate NFkappaB in human macrophages

Journal of Cellular Physiology
Anja GerthSunna Hauschildt

Abstract

Although much has been learned about signal transduction mechanisms and binding proteins involved in lipopolysaccharides (LPS)-induced activation of monocytes/macrophages, little is known about the ability of internalized LPS to activate cells. To approach this question we either exposed macrophages to LPS or microinjected the cells with LPS before studying early cellular events associated with LPS-mediated macrophage activation. We measured membrane currents and translocation of NFkappaB to the nucleus. Using the whole-cell patch clamp technique ion channels were analyzed and characterized as K+ sensitive inward and outward currents. Exogenous LPS was shown to increase the voltage-dependent outward current whereas the voltage-dependent inward current was unaffected. However when cells were microinjected with LPS both inward and outward current were completely abolished. The presence of LPS within the cells did not prevent them to perform phagocytosis or to respond to fMLP with an appropriate increase in [Ca2+]i. The immunocytological detection of NFkappaB p65 translocation revealed that exogenous LPS led to the nuclear localization of the p65 subunit of NFkappaB, whereas only the cytoplasmic localization of p65 was observed fo...Continue Reading

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Citations

Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Elizabeth IrvineHuangui Xiong
Nov 27, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Howard E GendelmanHuangui Xiong
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May 18, 2006·The Journal of Pharmacology and Experimental Therapeutics·Gerd BirkenmeierAngelika Schäfer
Jun 23, 2020·PLoS Biology·Patrick NeubertJonathan Jantsch

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