Chlamydia pneumoniae induces nitric oxide synthase and lipoxygenase- dependent production of reactive oxygen species in platelets

Abstract

SummaryThereisincreasing evidence that Chlamydia pneumoniae is linked to atherosclerosis and thrombosis. In this regard, we have recentlyshown that C.pneumoniae stimulates plateletaggregation and secretion, which mayplayanimportantrole in theprogress of atherosclerosisa nd in thrombotic vascular occlusion. The aims of thep resent study were to investigate thee ffects of C. pneumoniae on platelet-mediated formation of reactive oxygen species(ROS) and oxidationoflow-density lipoprotein (LDL) in vitro.R OS production was registereda sc hanges in 2´,7`-dichlorofluorescin-fluorescence in platelets with flowc ytometry. LDL-oxidationw as determinedb ym easuring thiobarbituric acid reactive substances (TBARs). We found that C.pneumoniae stimulated plateletproduction of ROS.Polymyxin Btreatment of C. pneumoniae,b ut not elevatedt emperature,a bolishedt he stimulatory effects on plateletROS-production, which suggests that chlamydial lipopolysaccharideh as an importantr ole.I n- KeywordsAtherosclerosis, bacteria-cell interaction,o xygen radical,L PS, thrombosis hibitionofnitric oxidesynthase with nitro-L-arginine,lipoxygenasew ith 5,8,11-eicosatriynoic acid and protein kinaseCwith GF 109203X significantlylowered the production of radicals. In contrast, inhibition of NADPH-oxidase with di-phenyleneiodonium(DPI) didnot affectthe C. pneumoniae induced ROS-production.Thesefindingssuggestthat the activities of nitric oxide synthase andlipoxygenase arethe sources forROS and that the generation is dependent of theactivity of protein kinaseC.The C.pneumoniae-induced ROS-production in platelets was associatedwith an extensiveoxidationofLDL,which wassignificantly highercompared to the effect obtainedbyseparate exposureof LDLto C. pneumoniae or platelets.Inconclusion, C. pneumoniae interactionw ith platelets leading to aggregation,ROS-production and oxidativedamage on LDL, mayplayacrucial role in the developmentofatherosclerotic cardiovascular disease.

Reactive oxygen and nitrogen species modulate the ex-vivo effects of LPS on platelet adhesion to fibrinogen

“…Previous works have shown that Chlamydia pneumoniae and Proteus mirabilis LPS induce an enhancement of ROS production in platelets (Kälvegren et al, 2005;Zielinski et al, 2001;Saluk-Juszczak et al, 2000). Consistent with these studies, our results showed that incubation of non-activated platelets with PEG-SOD restored the stimulatory effect of LPS, indicating that ROS such as O 2 − take part in this effect.…”

Circulating Chlamydia pneumoniae DNA and advanced coronary artery disease

“…Evidence obtained from animal models suggests that infection with C. pneumoniae contributes to atherogenesis and progression of atherosclerosis [5,6,37]. More recently, Chesebro et al [38] suggested a role for the inducible nitric oxide synthase (iNOS) to protect against development of fatty streak formation in hyperlipidemic mice inoculated intranasally with C. pneumoniae, while Kalvegren et al showed that C. pneumoniae may play an important role in atherogenesis via platelet-mediated production of reactive oxygen species and low-density lipoprotein (LDL) oxidation [39]. Most notably, Sawayama et al [40] reported that C. pneumoniae infection reduced the effect of lipid-lowering therapy on carotid atherosclerosis, suggesting a possible role for this organism in the progression of atherosclerosis.…”

Enhancement of Reactive Oxygen Species Production and Chlamydial Infection by the Mitochondrial Nod-like Family Member NLRX1

“…7) ROS is generated mainly by NOX on the plasma membrane and mitochondria. Other studies have reported ROS production during chlamydial infection (30,31), but they did not identify the source of host cell-derived ROS production. In this study, we have demonstrated that ROS production during C. trachomatis infection of epithelial cells is due primarily to two sources: NOX enzymes and NLRX1.…”