Summary
There is increasing evidence that Chlamydia pneumoniae is linked to atherosclerosis and thrombosis. In this regard, we have recently shown
that C. pneumoniae stimulates platelet aggregation and secretion, which may play an important role in
the progress of atherosclerosis and in thrombotic vascular occlusion. The aims of
the present study were to investigate the effects of C. pneumoniae on platelet-mediated formation of reactive oxygen species (ROS) and oxidation of
low-density lipoprotein (LDL) in vitro. ROS production was registered as changes in
2‘,7’-dichlorofluorescin- fluorescence in platelets with flow cytometry. LDL-oxidation
was determined by measuring thiobarbituric acid reactive substances (TBARs). We found
that C. pneumoniae stimulated platelet production of ROS. Polymyxin B treatment of C. pneumoniae, but not elevated temperature, abolished the stimulatory effects on platelet ROS-
production, which suggests that chlamydial lipopolysaccharide has an important role.
Inhibition of nitric oxide synthase with nitro-L-arginine, lipoxygenase with 5,8,11-eicosatriynoic
acid and protein kinase C with GF 109203X significantly lowered the production of
radicals. In contrast, inhibition of NADPH-oxidase with di-phenyleneiodonium (DPI)
did not affect the C. pneumoniae induced ROS-production. These findings suggest that the activities of nitric oxide
synthase and lipoxygenase are the sources for ROS and that the generation is dependent
of the activity of protein kinase C. The C. pneumoniae-induced ROS-production in platelets was associated with an extensive oxidation of
LDL, which was significantly higher compared to the effect obtained by separate exposure
of LDL to C. pneumoniae or platelets. In conclusion, C. pneumoniae interaction with platelets leading to aggregation, ROS-production and oxidative damage
on LDL, may play a crucial role in the development of atherosclerotic cardiovascular
disease.
Keywords
Atherosclerosis - bacteria-cell interaction - oxygen radical - LPS - thrombosis
