Elicitation of reactive oxygen species in Chlamydia pneumoniae-stimulated macrophages: a Ca2+-dependent process involving simultaneous activation of NADPH oxidase and cytochrome oxidase genes.
Chlamydia pneumoniae, a respiratory pathogen implicated in the development and progress of atherosclerosis, is known to infect and survive in macrophages, despite macrophage producing reactive oxygen species (ROS). To gain insight into ROS generation in macrophages infected with C. pneumoniae and to explore factors accounting for their final levels and effect, we investigated the role of NADPH oxidase and cytochrome oxidase pathways in the production and modulation of ROS. We also determined the operational role of Ca2+ signaling in the process. Macrophages stimulated with C. pneumoniae exhibit early release of ROS via up-regulation of NADPH oxidase and cytochrome c oxidase activities. Increasing the dose of C. pneumoniae led to an increase in the expression of these enzymes gene production, which was accompanied by a significant up-regulation of their gene products, implying a probable activation of transcriptional and translational processes, respectively. The change in levels of free Ca2+, influx across plasma membrane and efflux from intracellular store into cytosol all exhibited a significant regulatory role on the ROS generation pathways in macrophages. The observed events were shown to be dependent on binding of C. pneumoniae to CD14 receptors of macrophages. The data reported here imply that macrophages infected with C. pneumoniae produce ROS through membrane-associated NADPH oxidase with oxidative phosphorylation levels depending on Ca2+ influx signals.
Azenabor
Anthony A
AA
Department of Health Sciences, Enderis Hall, University of Wisconsin, Milwaukee, WI 53211, USA. aazenabo@uwm.edu
Yang
Shoua
S
Job
Godwin
G
Adedokun
Olanrewaju O
OO
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D016993:Chlamydophila pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D003576:Electron Transport Complex IV; D002118:Calcium