CFTR-mediated halide transport in phagosomes of human neutrophils

Richard G. Painter, Luis Marrero, Gisele A. Lombard, Vincent G. Valentine, William M. Nauseef, Guoshun Wang

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Chloride serves as a critical component of innate host defense against infection, providing the substrate for MPO-catalyzed production of HOCl in the phagosome of human neutrophils. Here, we used halide-specific fluorescent sensors covalently coupled to zymosan particles to investigate the kinetics of chloride and iodide transport in phagosomes of human neutrophils. Using the self-ratioable fluorescent probe specific for chloride anion, we measured chloride dynamics within phagosomes in response to extracellular chloride changes by quantitative fluorescence microscopy. Under the experimental conditions used, normal neutrophils showed rapid phagosomal chloride uptake with an initial influx rate of 0.31 ± 0.04 mM/s (n=5). GlyH-101, a CFTR inh, decreased the rate of uptake in a dose-dependent manner. Neutrophils isolated from CF patients showed a significantly slower rate of chloride uptake by phagosomes, having an initial influx rate of 0.043 ± 0.012 mM/s (n=5). Interestingly, the steady-state level of chloride in CF phagosomes was ∼26 mM, significantly lower than that of the control (∼68 mM). As CFTR transports chloride as well as other halides, we conjugated an iodide-sensitive probe as an independent approach to confirm the results. The dynamics of iodide uptake by neutrophil phagosomes were monitored by flow cytometry. CFTRinh172 blocked 40-50% of the overall iodide uptake by phagosomes in normal neutrophils. In a parallel manner, the level of iodide uptake by CF phagosomes was only 20-30% of that of the control. Taken together, these results implicate CFTR in transporting halides into the phagosomal lumen.

Original languageEnglish (US)
Pages (from-to)933-942
Number of pages10
JournalJournal of Leukocyte Biology
Issue number5
StatePublished - May 2010
Externally publishedYes


  • Chloride sensor
  • Fluorescent halide probes
  • Hypochlorous acid
  • Iodide sensor
  • Ion transport

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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