title: C. pneumoniae disrupts eNOS trafficking and impairs NO production in human aortic endothelial cells.
abstract: Endothelial nitric oxide synthase (eNOS) generated NO plays a crucial physiological role in the regulation of vascular tone. eNOS is a constitutively expressed synthase whose enzymatic function is regulated by dual acylation, phosphorylation, protein-protein interaction and subcellular localization. In endothelial cells, the enzyme is primarily localized to the Golgi apparatus (GA) and the plasma membrane where it binds to caveolin-1. Upon stimulation, the enzyme is translocated from the plasma membrane to the cytoplasm where it generates NO. When activation of eNOS ceases, the majority of the enzyme is recycled back to the membrane fraction. An inability of eNOS to cycle between the cytosol and the membrane leads to impaired NO production and vascular dysfunction. Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that primarily infects epithelial cells of the human respiratory tract, but unlike any other chlamydial species, C. pneumoniae displays tropism toward atherosclerotic tissues. In this study, we demonstrate that C. pneumoniae inclusions colocalize with eNOS, and the microorganism interferes with trafficking of the enzyme from the GA to the plasma membrane in primary human aortic endothelial cells. This mislocation of eNOS results in significant inhibition of NO release by C. pneumoniae-infected cells. Furthermore, we show that the distribution of eNOS in C. pneumoniae-infected cells is altered due to an intimate association of the Golgi complex with chlamydial inclusions rather than by direct interaction of the enzyme with the chlamydial inclusion membrane.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, 40536, USA.
authors.forename: Konrad E
authors.initials: KE
authors.lastname: Mueller
authors.forename: Katerina
authors.initials: K
authors.lastname: Wolf
mesh_terms: D002478:Cells, Cultured; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology* / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors*
chemical_list: D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III