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Phagosomal chloride dynamics in the alveolar macrophage
Acidification in intracellular organelles is tightly linked to the influx of Cl(−) counteracting proton translocation by the electrogenic V-ATPase. We quantified the dynamics of Cl(−) transfer accompanying cargo incorporation into single phagosomes in alveolar macrophages (AMs). Phagosomal Cl(−) con...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733233/ https://www.ncbi.nlm.nih.gov/pubmed/35024579 http://dx.doi.org/10.1016/j.isci.2021.103636 |
Sumario: | Acidification in intracellular organelles is tightly linked to the influx of Cl(−) counteracting proton translocation by the electrogenic V-ATPase. We quantified the dynamics of Cl(−) transfer accompanying cargo incorporation into single phagosomes in alveolar macrophages (AMs). Phagosomal Cl(−) concentration and acidification magnitude were followed in real time with maximal acidification achieved at levels of approximately 200 mM. Live cell confocal microscopy verified that phagosomal Cl(−) influx utilized predominantly the Cl(−) channel CFTR. Relative levels of elemental chlorine (Cl) in hard X-ray fluorescence microprobe (XFM) analysis within single phagosomes validated the increase in Cl(−) content. XFM revealed the complex interplay between elemental K content inside the phagosome and changes in Cl(−) during phagosomal particle uptake. Cl(−) -dependent changes in phagosomal membrane potential were obtained using second harmonic generation (SHG) microscopy. These studies provide a mechanistic insight for screening studies in drug development targeting pulmonary inflammatory disease. |
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