FcγRI, the human high-affinity IgG receptor, is responsible for the internalization of immune complexes and their subsequent targetting to the lysosomes for degradation. We show here that aggregation of FcγRI by surface immune complexes in interferon-γ-primed U937 cells causes the transient appearance of swollen vacuolar structures, probably swollen late endosomes, which disappear as the immune complexes are degraded. Wortmannin and LY294002, specific inhibitors of phosphoinositide 3-kinases (PI 3-kinases), delay the disappearance of these structures and also correspondingly inhibit degradation of FcγRI-mediated immune complexes. In addition these inhibitors delay the initial phase of FcγRI-mediated endocytosis of immune complexes and block the activity of FcγRI-stimulated phospholipase D, an enzyme that has previously been implicated in membrane-trafficking events. p85 is the regulatory subunit of PI 3-kinase. A p85-dependent PI 3-kinase was shown to be involved in the initial phase of FcγRI-mediated endocytosis, but not in the trafficking of immune complexes for degradation or the activation of phospholipase D. The results presented here show a role for a p85-independent PI 3-kinase in regulating the trafficking of FcγRI-mediated immune complexes, either directly or as a result of the activation of phospholipase D, and a distinct role for a p85-dependent PI 3-kinase isoform in the initial phases of FcγRI-mediated internalization of immune complexes.
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December 1999
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Research Article|
November 24 1999
Endocytosis and vesicular trafficking of immune complexes and activation of phospholipase D by the human high-affinity IgG receptor requires distinct phosphoinositide 3-kinase activities
David J. GILLOOLY;
*Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
†Department of Medicine and Therapeutics, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
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Alirio J. MELENDEZ;
*Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
†Department of Medicine and Therapeutics, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
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Austin R. HOCKADAY;
Austin R. HOCKADAY
‡Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, U.K.
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Margaret M. HARNETT;
Margaret M. HARNETT
§Department of Immunology, University of Glasgow, Western Infirmary, Glasgow G11 6NT, Scotland, U.K.
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Janet M. ALLEN
Janet M. ALLEN
4
*Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
†Department of Medicine and Therapeutics, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
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Publisher: Portland Press Ltd
Received:
June 21 1999
Revision Received:
September 09 1999
Accepted:
September 27 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 344 (2): 605–611.
Article history
Received:
June 21 1999
Revision Received:
September 09 1999
Accepted:
September 27 1999
Citation
David J. GILLOOLY, Alirio J. MELENDEZ, Austin R. HOCKADAY, Margaret M. HARNETT, Janet M. ALLEN; Endocytosis and vesicular trafficking of immune complexes and activation of phospholipase D by the human high-affinity IgG receptor requires distinct phosphoinositide 3-kinase activities. Biochem J 1 December 1999; 344 (2): 605–611. doi: https://doi.org/10.1042/bj3440605
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