Effective macrophage redox defense against Chlamydia pneumoniae depends on L-type Ca2+ channel activation.
Macrophage immune capability depends on their efficient redox potential expressed in the effective release of reactive oxygen species (ROS) and nitric oxide. In this study the effect of the activation of a specialized Ca(2+) channel on macrophage redox function during Chlamydia pneumoniae infection was explored. C. pneumoniae exhibited a profound and sustained Ca(2+) influx capacity, with evidence of activity attributable to their lipopolysaccharide (cLPS) content. Also the organism showed an additional Ca(2+) influx signal in macrophages exposed to thapsigargin, and there was evidence for the operation of a single ion channel of the L type as demonstrated by the effect of L-type channel antagonists (methoxyverapamil and nimodipine) despite exposure to Ca(2+)-rich medium. C. pneumoniae or cLPS induced intracellular ROS and NO generation in a manner consistent with dependence on intracellular calcium. L-type Ca(2+) channel blocking significantly prompted C. pneumoniae inclusion formation. These findings suggest that Ca(2+) influx signal and redox function in C. pneumoniae-infected macrophages depend on L-type Ca(2+) channel activation.
Azenabor
Anthony A
AA
Department of Health Sciences, Enderis Hall, Room 469, University of Wisconsin, 2400 E. Hartford Avenue, Milwaukee WI 53211, USA. aazenabo@uwm.edu
Chaudhry
Aziz U
AU
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism* / Q000502:physiology; D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D009589:Nitrogen Oxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D002118:Calcium