title: Chlamydophila pneumoniae derived from inclusions late in the infectious cycle induce aponecrosis in human aortic endothelial cells.
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 death 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 protein 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.
authors.affiliation: Division of Cell Biology, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. joseph_marino@access.unizh.ch
authors.forename: Joseph
authors.initials: J
authors.lastname: Marino
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stoeckli
authors.forename: Michael
authors.initials: M
authors.lastname: Walch
authors.forename: Sonja
authors.initials: S
authors.lastname: Latinovic-Golic
authors.forename: Hanna
authors.initials: H
authors.lastname: Sundstroem
authors.forename: Peter
authors.initials: P
authors.lastname: Groscurth
authors.forename: Urs
authors.initials: U
authors.lastname: Ziegler
authors.forename: Claudia
authors.initials: C
authors.lastname: Dumrese
mesh_terms: D001011:Aorta; D017209:Apoptosis; D050197:Atherosclerosis / Q000382:microbiology*; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D018834:Chaperonin 60 / Q000378:metabolism; D023521:Chlamydophila Infections / Q000382:microbiology* / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000382:microbiology*; D009336:Necrosis / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D024243:HMGB1 Protein