A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial lipopolysaccharide.
Chlamydia pneumoniae infection is associated with atherosclerotic heart and vessel disease, but a causal relationship between this pathogen and the disease process has not been established. Recently, it was reported that C. pneumoniae induces human macrophage foam cell formation, a key event in early atheroma development, suggesting a role for the organism in atherogenesis. This study further examines C. pneumoniae-induced foam cell formation in the murine macrophage cell line RAW-264.7. Infected RAW cells accumulated cholesteryl esters when cultured in the presence of low-density lipoprotein in a manner similar to that described for human macrophages. Exposure of C. pneumoniae elementary bodies to periodate, but not elevated temperatures, inhibited cholesteryl ester accumulation, suggesting a role for chlamydial lipopolysaccharide (cLPS) in macrophage foam cell formation. Purified cLPS was found to be sufficient to induce cholesteryl ester accumulation and foam cell formation. Furthermore, the LPS antagonist lipid X inhibited C. pneumoniae and cLPS-induced lipid uptake. These data indicate that cLPS is a C. pneumoniae component that induces macrophage foam cell formation and suggest that infected macrophages chronically exposed to cLPS may accumulate excess cholesterol to contribute to atheroma development.
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
M V
MV
Kalayoglu
G I
GI
Byrne
D000818:Animals; D001161:Arteriosclerosis / Q000382:microbiology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016993:Chlamydophila pneumoniae / Q000737:chemistry / Q000502:physiology*; D002788:Cholesterol Esters / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology; D006017:Glycolipids / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D010504:Periodic Acid / Q000494:pharmacology; D013696:Temperature
D002788:Cholesterol Esters; D006017:Glycolipids; D006131:Growth Inhibitors; D008070:Lipopolysaccharides; D010504:Periodic Acid; C044283:lipid X; C009288:metaperiodate