Characterization of low-density lipoprotein uptake by murine macrophages exposed to Chlamydia pneumoniae.
Exposure to Chlamydia pneumoniae is correlated with atherosclerosis in a variety of clinical and epidemiological studies, but how the organism may initiate and promote the disease is poorly understood. One pathogenic mechanism could involve modulation of macrophage function by C. pneumoniae. We recently demonstrated that C. pneumoniae induces macrophages to accumulate excess cholesterol and develop into foam cells, the hallmark of early atherosclerotic lesions. To determine if C. pneumoniae-induced foam cell formation involved increased uptake of low-density lipoprotein (LDL), the current study examined macrophage association of a fluorescent carbocyanine (DiI)-labeled LDL following infection. C. pneumoniae enhanced the association of DiI-LDL with macrophages in a dose-dependent manner with respect to both C. pneumoniae and DiI-LDL. Interestingly, increased association was inhibited by native LDL and occurred in the absence of oxidation byproducts and in the presence of antioxidants. However, enhanced DiI-LDL association occurred without the participation of the classical Apo B/E native LDL receptor, since C. pneumoniae increased DiI-LDL association and induced foam cell formation in macrophages isolated from LDL-receptor-deficient mice. Surprisingly, DiI-LDL association was inhibited not only by unlabeled native LDL but also by high-density lipoprotein, very low density lipoprotein, and oxidized LDL. These data indicate that exposure of macrophages to C. pneumoniae increases the uptake of LDL and foam cell formation by an LDL-receptor-independent mechanism.
Kalayoglu
M V
MV
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, USA.
Miranpuri
G S
GS
Golenbock
D T
DT
Byrne
G I
GI
D000818:Animals; D002232:Carbocyanines / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D005453:Fluorescence; D005487:Foam Cells / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002232:Carbocyanines; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011973:Receptors, LDL