CFTR regulates phagosome acidification in macrophages and alters bactericidal activity
| Autor: | Vytautas P. Bindokas, Anjaparavanda P. Naren, H. Clive Palfrey, Frances L. Szeto, Chunying Li, Yimei Chen, Anke Di, Jiankun Tong, Michael Brown, Deborah J. Nelson, Ludmila V. Deriy, Ping Huang |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Neutrophils Phagosome acidification Phagocytosis Cystic Fibrosis Transmembrane Conductance Regulator In Vitro Techniques Microbiology Mice Immune system Phagosomes Macrophages Alveolar Cyclic AMP Animals Humans Respiratory Burst Phagosome Mice Knockout Microbial Viability Innate immune system biology Macrophages Cell Biology Hydrogen-Ion Concentration respiratory system biology.organism_classification Cystic fibrosis transmembrane conductance regulator Cell biology Respiratory burst Mice Inbred C57BL Pseudomonas aeruginosa Macrophages Peritoneal biology.protein Lysosomes Ion Channel Gating Bacteria |
| Zdroj: | Nature Cell Biology. 8:933-944 |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb1456 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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