Characterization of low-density lipoprotein uptake by murine macrophages exposed to Chlamydia pneumoniae

Exposure to Chlamydia pneumoniae is correlated with atherosclerosis in a va riety of clinical and epidemiological studies, but how the organism may ini tiate and promote the disease is poorly understood. One pathogenic mechanis m could involve modulation of macrophage function by C, pneumoniae. We rece ntly demonstrated that C, pneumoniae induces macrophages to accumulate exce ss cholesterol and develop into foam cells, the hallmark of early atheroscl erotic lesions. To determine if C, pneumoniae-induced foam cell formation i nvolved increased uptake of low-density lipoprotein (LDL), the current stud y examined macrophage association of a fluorescent carbocyanine (DiI)-label ed LDL following infection. C, pneumoniae enhanced the association of DiI-L DL with macrophages in a dose-dependent manner with respect to both C, pneu moniae and DiI-LDL. Interestingly, increased association was inhibited by n ative LDL and occurred in the absence of oxidation byproducts and in the pr esence of antioxidants. However, enhanced DiI-LDL association occurred with out 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 b y high-density lipoprotein, very low density lipoprotein, and oxidized LDL. These data indicate that exposure of macrophages to C, pneumoniae increase s the up take of LDL and foam cell formation by an LDL-receptor-independent mechanism. (C) Elsevier, Paris.