Differential trafficking of oxidized LDL and oxidized LDL immune complexes in macrophages: impact on oxidative stress.
BACKGROUND
Oxidized low-density lipoproteins (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to formation of lipid-laden macrophages (foam cells). It has been shown that oxLDL-IC are considerably more efficient than oxLDL in induction of foam cell formation, inflammatory cytokines secretion, and cell survival promotion. Whereas oxLDL is taken up by several scavenger receptors, oxLDL-IC are predominantly internalized through the FCgamma receptor I (FCgamma RI). This study examined differences in intracellular trafficking of lipid and apolipoprotein moieties of oxLDL and oxLDL-IC and the impact on oxidative stress.


RESULTS
Fluorescently labeled lipid and protein moieties of oxLDL co-localized within endosomal and lysosomal compartments in U937 human monocytic cells. In contrast, the lipid moiety of oxLDL-IC was detected in the endosomal compartment, whereas its apolipoprotein moiety advanced to the lysosomal compartment. Cells treated with oxLDL-IC prior to oxLDL demonstrated co-localization of internalized lipid moieties from both oxLDL and oxLDL-IC in the endosomal compartment. This sequential treatment likely inhibited oxLDL lipid moieties from trafficking to the lysosomal compartment. In RAW 264.7 macrophages, oxLDL-IC but not oxLDL induced GFP-tagged heat shock protein 70 (HSP70) and HSP70B', which co-localized with the lipid moiety of oxLDL-IC in the endosomal compartment. This suggests that HSP70 family members might prevent the degradation of the internalized lipid moiety of oxLDL-IC by delaying its advancement to the lysosome. The data also showed that mitochondrial membrane potential was decreased and generation of reactive oxygen and nitrogen species was increased in U937 cell treated with oxLDL compared to oxLDL-IC.


CONCLUSIONS
Findings suggest that lipid and apolipoprotein moieties of oxLDL-IC traffic to separate cellular compartments, and that HSP70/70B' might sequester the lipid moiety of oxLDL-IC in the endosomal compartment. This mechanism could ultimately influence macrophage function and survival. Furthermore, oxLDL-IC might regulate the intracellular trafficking of free oxLDL possibly through the induction of HSP70/70B'.
Al Gadban
Mohammed M
MM
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America.
Smith
Kent J
KJ
Soodavar
Farzan
F
Piansay
Christabelle
C
Chassereau
Charlyne
C
Twal
Waleed O
WO
Klein
Richard L
RL
Virella
Gabriel
G
Lopes-Virella
Maria F
MF
Hammad
Samar M
SM
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D045744:Cell Line, Tumor; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress; D021381:Protein Transport
D000936:Antigen-Antibody Complex; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein
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