Kinetic Separation of Oxidative and Non-oxidative Metabolism in Single Phagosomes from Alveolar Macrophages: Impact on Bacterial Killing

iScience

Zihao Sui¹  Deborah J. Nelson²  Vladimir Riazanski² 

[1] Corresponding author;The University of Chicago, Department of Pharmacological and Physiological Sciences, 947 E. 58th Street, MC 0926, Chicago, IL 60637, USA;

关键词: Immunology;    Microbiology;    Cell Biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: The relative contribution of the two phagosomal catabolic processes, oxidative and metabolic, was assessed in the killing of Pseudomonas aeruginosa in phagosomes of alveolar macrophages (AMs) from wild-type (p47-phox+/+) or NOX-defective (p47-phox−/−) mice. Free radical release and degradative acidification within AM phagosomes is sequential and separable. The initial NOX activity, identifiable as a transient alkalinization, leads to fast bacterial wall permeabilization by ROS. This is followed by V-ATPase-induced acidification and enzymatic bacterial degradation contributed through phagosomal-lysosomal fusion. The alkalinization/acidification ratio was variable among phagosomes within single cells of a given genotype and not as a function of macrophage M1 or M2 classification, possibly owing to uneven distribution of phagosomal transporter proteins. Irregular, excessive NOX activity prevents phago-lysosomal fusion, and the lack of V-ATPase-induced acidification leads to bacterial stasis in the phagosome. Thus, efficient phagosomal bacterial killing is a result of tightly balanced activity between two processes.

【 授权许可】

Unknown