CFTR regulates phagosome acidification in macrophages and alters bactericidal activity.
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.
Di
Anke
A
Dept. of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA.
Brown
Mary E
ME
Deriy
Ludmila V
LV
Li
Chunying
C
Szeto
Frances L
FL
Chen
Yimei
Y
Huang
Ping
P
Tong
Jiankun
J
Naren
Anjaparavanda P
AP
Bindokas
Vytautas
V
Palfrey
H Clive
HC
Nelson
Deborah J
DJ
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008247:Lysosomes / Q000502:physiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000382:microbiology / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050296:Microbial Viability; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D016897:Respiratory Burst
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP