BMC Microbiol. 2008 Feb 19;8(1):32 [Epub ahead of print]
Chlamydophila pneumoniae derived from inclusions late in the infectious cycle induce aponecrosis in human aortic endothelial cells.
Marino J, Stoeckli I, Walch M, Latinovic-Golic S, Sundstrom H, Groscurth P, Ziegler U, Dumrese C.
ABSTRACT: BACKGROUND: Atherosclerosis is still the leading cause of death in the western world. Besides known risk factors studies demonstrating Chlamydophila pneumoniae (C. pneumoniae) to be implicated in the progression of the disease, little is known about C. pneumoniae infection dynamics. We investigated whether C. pneumoniae induce cell deathi of human aortic endothelial cells, a cell type involved in the initiation of atherosclerosis, and whether chlamydial spots derive from inclusions.
RESULTS: Lactate dehydrogenase release revealed host cell death to be dependent on the amounts of Chlamydia used for infection. The morphology of lysed human aortic endothelial cells showed DNA strand breaks simultaneously with cell membrane damage exclusively in cells carrying Chlamydia as spots. Further ultrastructural analysis revealed additional organelle dilation, leading to the definition as aponecrotic cell death of endothelial cells. Exclusive staining of the metabolic active pathogens by chlamydial heat shock proteini 60 labelling and ceramide incorporation demonstrated that the bacteria responsible for the induction of aponecrosis had resided in former inclusions. Furthermore, a strong pro-inflammatory molecule, high mobility group box protein 1, was shown to be released from aponecrotic host cells.
CONCLUSIONS: From the data it can be concluded that aponecrosis inducing C. pneumoniae stem from inclusions, since metabolically active bacterial spots are strongly associated with aponecrosis late in the infectious cycle in vascular endothelial cells and metabolic activity was exclusively located inside of inclusions in intact cells. Vice versa initial spot-like infection with metabolically inert bacteria does not have an effect on cell death induction. Hence, C. pneumoniae infection can contribute to atherosclerosis by initial endothelial damage.
PMID: 18284660 [PubMed - as supplied by publisher]
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Nelly (France-neuroLyme and ????)
Okay, but is it
Okay, but is it reversible?
Joyce~caregiver-advocate in Dallas for Steve J (SPMSi). CAPi since August 06, Cpni, Mpn, B. burgdorferi, systemic candidiasis, EBVi, CMV & other herpes family viral infectionsi, elevated heavy metals, gluten+casein sensitivity.
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Joyce~caregiver-advocate in Dallas for Steve J (SPMSi). CAPi since August 06, Cpni, Mpn, B. burgdorferi, systemic candidiasis, EBVi, CMV & other herpes family viral infectionsi, elevated heavy metals, gluten+casein sensitivity.
My question as well, as I
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Nelly (France-neuroLyme and ????)
Can anyone summarize that
Can anyone summarize that for me in plain English? LOL
Asthmai, chronic sinusitis/rhinitis, chronic tendonitis, hypothyroid. Jan 9, '08 started Azithromycin 1000mg/week.
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GFAi - asthmai, sinusitis/rhinitis, tendonitis, low back pain, hypothyroid. Started azi 1000mg/week Jan 9, '08. Increased azi to 250mg/day, added 20mg Benicar daily Mar 13, '08. First Flagyli pulse started June 30, '08. Added Doxyi 200mg/day Aug 16.
Hi Nelly- I saw this one too
Hi Nelly- I saw this one too but hadn't digested it.
Doing this as much as an exercise to clarify this one for myself as for anyone else. Chime in if I have this wrong, please.
Basically, this is an attempt to look at how Cpni might be contributing to Atherosclerosis. It has been linked, and found in plaques, but a lot of controversy surrounds it scientifically as to whether it is a secondary or primary event for the disease. Since necrosisi of cardiac endothelial cells occurs in Atherosclerosis, they looked at the impact of Cpn infection on these cells to understand the pathways by which Cpn could be affecting necrosis.
We investigated whether C. pneumoniae induce cell deathii of human aortic endothelial cells, a cell type involved in the initiation of atherosclerosis, and whether chlamydial spots derive from inclusions.
RESULTS: Lactate dehydrogenase release revealed host cell death to be dependent on the amounts of Chlamydia used for infection. Whether host cells died (apoptosis) depended on the amount of Cpn used to infect the cell cultures. The morphology of lysed human aortic endothelial cells showed DNA strand breaks simultaneously with cell membrane damage exclusively in cells carrying Chlamydia as spots. Further ultrastructural analysis revealed additional organelle dilation, leading to the definition as aponecrotic cell death of endothelial cells. Only Cpn infected cells showed DNA, cell membrane damage and additional signs consistent with the definition of aponecrosis (degradation of tissue from apoptosis). Exclusive staining of the metabolic active pathogens by chlamydial heat shock proteinii 60 labelling and ceramide incorporation demonstrated that the bacteria responsible for the induction of aponecrosis had resided in former inclusions. I think this is just another confirmation that the bacteria responsible is Cpn as Cpn characteristically infects the host cell by residing in an inclusion membrane within the cell. Furthermore, a strong pro-inflammatory molecule, high mobility group box protein 1, was shown to be released from aponecrotic host cells. The dead host cells release inflammatory proteins.
CONCLUSIONS: From the data it can be concluded that aponecrosis inducing C. pneumoniae stem from inclusions, since metabolically active bacterial spots are strongly associated with aponecrosis late in the infectious cycle in vascular endothelial cells and metabolic activity was exclusively located inside of inclusions in intact cells. Vice versa initial spot-like infection with metabolically inert bacteria does not have an effect on cell death induction. Hence, C. pneumoniae infection can contribute to atherosclerosis by initial endothelial damage.
This last seems to be confirming that it is Cpn and not some other agent responsible for the necrosis.
This is a basic science study, not a clinical one, arguing for the direct link of Cpn and necrosis of cardiac endothelial cells in Arteriosclerosis. It really doesn't have anything to say about the possibility of cell replacement or repair, although obviously if necrosis damages a wider swath of tissue (and induces more in neighboring celss by releasing inflammatory cytokinesi-- a fact already known in Cpn induction of necrosis), you won't get much repair of the necrosed tissue.
CAPi for Cpn 11/04. Dx: 25yrs CFSi & FMSi. Protocol: 200mg Doxyi, 500mg MWF Azith, Tinii 1000mg/day pulses; Vit D1000 units, INHi 150mg, Magnascent Iodine 20 drps/day, T4 & T3
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CAPi for Cpni 11/04. Dx: 25yrs CFSi & FMSi. Currently: 150mg BID Roxithromycin, Doxycycline 100mg BID, Tinii 1000mg/day pulses; Vit D2000 units, T4 & T3