CFTR targeting during activation of human neutrophils

Hang Pong Ng, Vincent G. Valentine, Guoshun Wang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel, plays critical roles in phagocytic host defense. However, how activated neutrophils regulate CFTR channel distribution subcellularly is not well defined. To investigate, we tested multiple Abs against different CFTR domains, to examine CFTR expression in human peripheral blood neutrophils by flow cytometry. The data confirmed that resting neutrophils had pronounced CFTR expression. Activation of neutrophils with soluble or particulate agonists did not significantly increase CFTR expression level, but induced CFTR redistribution to cell surface. Such CFTR mobilization correlated with cell-surface recruitment of formyl-peptide receptor during secretory vesicle exocytosis. Intriguingly, neutrophils from patients with ΔF508-CF, despite expression of the mutant CFTR, showed little cell-surface mobilization upon stimulation. Although normal neutrophils effectively targeted CFTR to their phagosomes, ΔF508-CF neutrophils had impairment in that process, resulting in deficient hypochlorous acid production. Taken together, activated neutrophils regulate CFTR distribution by targeting this chloride channel to the subcellular sites of activation, and ΔF508-CF neutrophils fail to achieve such targeting, thus undermining their host defense function.

Original languageEnglish (US)
Pages (from-to)1413-1424
Number of pages12
JournalJournal of Leukocyte Biology
Volume100
Issue number6
DOIs
StatePublished - Dec 1 2016

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Neutrophil Activation
Neutrophils
Chloride Channels
Formyl Peptide Receptor
Hypochlorous Acid
Phagosomes
Exocytosis
Secretory Vesicles
Flow Cytometry

Keywords

  • Chloride channel
  • Cystic fibrosis
  • Hypochlorous acid oxidant
  • Neutrophil defect
  • Phagocytic host defense

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

CFTR targeting during activation of human neutrophils. / Ng, Hang Pong; Valentine, Vincent G.; Wang, Guoshun.

In: Journal of Leukocyte Biology, Vol. 100, No. 6, 01.12.2016, p. 1413-1424.

Research output: Contribution to journalArticle

Ng, Hang Pong ; Valentine, Vincent G. ; Wang, Guoshun. / CFTR targeting during activation of human neutrophils. In: Journal of Leukocyte Biology. 2016 ; Vol. 100, No. 6. pp. 1413-1424.
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