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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- on metabolism of lipoprotein immune complexes mediated by specific human macrophage Fc receptors

Correspondence to: Peter M. Morganelli

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

We conclude that there may be differences in cholesterol trafficking with respect to lipoprotein immune complex metabolism mediated by different classes of FcRs.—Morganelli, P. M., S. M. Kennedy, and T. I. Mitchell. Differential effects of interferon- on metabolism of lipoprotein immune complexes mediated by specific human macrophage Fc 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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