CFTR regulates phagosome acidification in macrophages and alters bactericidal activity

Nature Cell Biology 8, 933 - 944 (2006)

Speaker: 黃惠芝                        Place: Room 602

Commentator: 胥直利老師               Date: 2006/12/20 13:00-14:00

Abstract:

Phagocytosis plays an important step in killing microorganisms in innate immunity. Microbes are engulfed by phagocytes then combined with their vacuole to form phagosomes. The lysosomes fuse to phagosomes and release enzyme contents, which can digest pathogens in an acid environment. Cystic fibrosis transmembrane conductance regulator ( CFTR ) is chroride ion channel involving the salt transport often in a number of epithelia cells. The gene cftr discovered in 1989 were thought relative to cystic fibrosis. Cystic fibrosis patients usually die from chronic infection of lung diseases. Previous findings showed that the ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation.In this paper, the authors discovered the CFTR participated in regulating phagosomes acidification. The alveolar macrophages of the cftr-/- mice had deficient in bactericidal acidification activities of phagosomes and lysosomes respectively as compare to wild-type cells. These data revealed that the CFTR protein in phagosomes and lysosomes could result in an acidic environment that was favourable for bactericidal activity.

References

1. Neil A. Bradbury Intracellular CFTR: Localization and Function Physiological Reviews Vol. 79, Suppl., No. 1, January 1999

2. Hara-Chikuma, M. et al. ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation. J. Biol. Chem. 280, 1241–1247 (2005).