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J. Lipid Res.
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Journal of Lipid Research, Vol. 41, 405-415, March 2000
Copyright © 2000 by Lipid Research, Inc.


Original Article

Differential effects of interferon-{gamma} on metabolism of lipoprotein immune complexes mediated by specific human macrophage Fc{gamma} receptors

Peter M. Morganellia, Susan M. Kennedya, and Teresa I. Mitchella
a United States Department of Veterans Affairs, White River Junction, VT 05009, and Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756

Correspondence to: Peter M. Morganelli

The objectives were to determine whether there are differences in the mechanisms of lipoprotein metabolism associated with different Fc{gamma}Rs and how metabolism associated with Fc{gamma}Rs 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 Fc{gamma}RI or Fc{gamma}RIIA in human macrophages. Interferon-{gamma} (IFN-{gamma}), which stimulates expression of Fc{gamma}RI 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-{gamma}. In particular, while SRA-mediated degradation typically exceeded degradation mediated by Fc{gamma}RI, in IFN-{gamma}-treated cells degradation associated with Fc{gamma}RI 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-{gamma}. For Fc{gamma}RI versus Fc{gamma}RIIA, in the presence or absence of IFN-{gamma}, the [3H]cholesterol derived from Fc{gamma}RIIA-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-{gamma}.

We conclude that there may be differences in cholesterol trafficking with respect to lipoprotein immune complex metabolism mediated by different classes of Fc{gamma}Rs.—Morganelli, P. M., S. M. Kennedy, and T. I. Mitchell. Differential effects of interferon-{gamma} on metabolism of lipoprotein immune complexes mediated by specific human macrophage Fc{gamma} receptors. J. Lipid Res. 2000. 41: 405;–415.

Supplementary key words: Fc receptors, scavenger receptors, bispecific antibodies, gamma interferon, human macrophages, lipoproteins, lipoprotein metabolism, cholesterol metabolism, cholesterol linoleate, cholesterol trafficking


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