The uptake of LDL-IC by human macrophages: predominant involvement of the Fc gamma RI receptor.
The incubation of human macrophages with antigen antibody complexes prepared with rabbit anti-LDL and human LDL (LDL-IC) is followed by ingestion of those immune complexes (IC), massive cholesterol ester accumulation, cytokine release and overexpression of the LDL receptor. The massive accumulation of cholesterol esters and overexpression of the native LDL receptor are specifically induced by immune complexes containing native or modified LDL, but not by any other type of IC. We report the results of a series of experiments aimed at defining the receptor preferentially involved in LDL-IC uptake. Flow cytometry studies using CD16, CD32 and CD64 monoclonal antibodies showed a sharp reduction on the expression of CD64 (Fc gamma RI) both by human monocyte-derived macrophages and THP-1 cells after incubation with LDL-IC, suggesting preferential engagement of this type of Fc receptor. Blocking experiments with aggregate-free IgG1 and CD32 monoclonal antibody confirmed that blocking Fc gamma RI prevented both LDL-IC uptake and the upregulation of LDL receptors on THP-1 cells. In contrast, blocking Fc gamma RII did not affect either the uptake of LDL-IC or the expression of LDL receptors on the same cells. The preferential engagement of Fc gamma R-I by LDL-IC suggests a biological difference of LDL-IC relative to other types of IC and opsonized particles. The precise molecular mechanism(s) responsible for the paradoxical upregulation of LDL receptor after the uptake of LDL-IC remain to be elucidated.
Lopes-Virella
M F
MF
Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC 29403, USA.
Binzafar
N
N
Rackley
S
S
Takei
A
A
La Via
M
M
Virella
G
G
D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D011973:Receptors, LDL / Q000096:biosynthesis
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D008077:Lipoproteins, LDL; D017452:Receptors, IgG; D011973:Receptors, LDL