出版社:American Society for Biochemistry and Molecular Biology
摘要:The objectives were to determine whether there are differences in the mechanisms of lipoprotein metabolism associated with different FcγRs and how metabolism associated with FcγRs compares to that mediated by scavenger receptors (SRA). To analyze lipoprotein metabolism in a receptor-specific manner, bispecific antibodies were used to target low density lipoproteins (LDL) labeled with 125I or [3H]cholesterol linoleate to FcγRI or FcγRIIA in human macrophages. Interferon-γ (IFN-γ), which stimulates expression of FcγRI while inhibiting expression of SRA, was used to help delineate differences in metabolism between each receptor. For each receptor, the total amount of lipoprotein degradation paralleled changes in receptor expression induced by IFN-γ. In particular, while SRA-mediated degradation typically exceeded degradation mediated by FcγRI, in IFN-γ-treated cells degradation associated with FcγRI and SRA was similar. Assay of [3H]cholesterol linoleate-labeled lipoproteins indicated that total uptake and hydrolysis of [3H]cholesterol linoleate was similar for each class of receptor, and inhibited by IFN-γ. For FcγRI versus FcγRIIA, in the presence or absence of IFN-γ, the [3H]cholesterol derived from FcγRIIA-mediated uptake was preferentially targeted for re-esterification to [3H]cholesterol oleate, in comparison to that resulting from hydrolysis of [3H]cholesterol linoleate incorporated by selective uptake. For SRA, the formation of [3H]cholesterol oleate, which was substantial in control cells, was significantly inhibited in the presence of IFN-γ. We conclude that there may be differences in cholesterol trafficking with respect to lipoprotein immune complex metabolism mediated by different classes of FcγRs. —Morganelli, P. M., S. M. Kennedy, and T. I. Mitchell. Differential effects of interferon-γ on metabolism of lipoprotein immune complexes mediated by specific human macrophage Fcγ receptors. J. Lipid Res. 2000. 41: 405–415.