Article abstract
Nature Cell Biology 8, 933 - 944 (2006)
Published online: 20 August 2006 | doi:10.1038/ncb1456
CFTR regulates phagosome acidification in macrophages and alters bactericidal activity
Anke Di1, Mary E. Brown1, Ludmila V. Deriy1, Chunying Li2, Frances L. Szeto1, Yimei Chen3, Ping Huang1, Jiankun Tong4, Anjaparavanda P. Naren2, Vytautas Bindokas1, H. Clive Palfrey1 & Deborah J. Nelson1
Abstract
Acidification of phagosomes has been proposed to have a key role in the microbicidal function of phagocytes. Here, we show that in alveolar macrophages the cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) participates in phagosomal pH control and has bacterial killing capacity. Alveolar macrophages from Cftr-/- mice retained the ability to phagocytose and generate an oxidative burst, but exhibited defective killing of internalized bacteria. Lysosomes from CFTR-null macrophages failed to acidify, although they retained normal fusogenic capacity with nascent phagosomes. We hypothesize that CFTR contributes to lysosomal acidification and that in its absence phagolysosomes acidify poorly, thus providing an environment conducive to bacterial replication.
- Dept. of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA.
- Department of Physiology, University of Tennessee-Memphis, 894 Union Avenue 420 Nash, Memphis, TN 38163, USA.
- Dept. of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
- Dept. of Medicine, University of Chicago, Chicago, IL 60637, USA.
Correspondence to: Deborah J. Nelson1 e-mail: nelson@uchicago.edu
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