title: Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci.
abstract: Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of 'infectious burden' in the development and progression of atherosclerosis.
authors.affiliation: Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: Shankar J
authors.initials: SJ
authors.lastname: Evani
authors.affiliation: Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Ramasubramanian
mesh_terms: D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology*; D055592:Biophysical Phenomena; D002448:Cell Adhesion; D002633:Chemotaxis; D016993:Chlamydophila pneumoniae / Q000502:physiology*; D008078:Cholesterol, LDL / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D036904:Leukocyte Rolling; D008560:Membrane Fluidity; D021962:Membrane Microdomains / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D058226:Plaque, Atherosclerotic
chemical_list: D008078:Cholesterol, LDL; D019040:E-Selectin; D018960:Hyaluronan Receptors