| The influence of IgG density and macrophage Fc (gamma) receptor cross-linking on phagocytosis and IL-10 production. | |
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MedLine Citation:
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PMID: 20670655 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously demonstrated that the addition of immune complexes (IC) to stimulated macrophages could profoundly influence cytokine production. In the present work we sought to determine the density of IgG on immune complexes necessary to mediate phagocytosis, inhibit IL-12 production and induce IL-10 production from stimulated macrophages. We developed immune complexes with predictable average densities of surface-bound immunoglobulin. We show that a threshold amount of IgG was necessary to mediate attachment of IC to macrophages. At progressively higher densities of IgG, Fc receptor-mediated phagocytosis resulted in an inhibition of IL-12 production and then an induction of IL-10. The reciprocal alterations in these two cytokines occurred when as little as one optimally opsonized SRBC was bound per macrophage. Macrophage IL-10 induction by immune complexes was associated with the activation of the MAP kinase, ERK, which was progressively increased as a function of IgG density. We conclude that signal transduction through the macrophage Fcγ receptors vary as a function of signal strength. At moderate IgG densities, especially in the presence of complement, efficient phagocytosis occurs in the absence of cytokine alterations. At slightly higher IgG densities IL-12 production is shut off and eventually IL-10 induction occurs. Thus, the myriad events emanating from FcγR ligation depends on the density of immune complexes, allowing the Fc receptors to fine-tune cellular responses depending on the extent of receptor cross-linking. |
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Authors:
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Paul Gallo; Ricardo Gonçalves; David M Mosser |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-27 |
Journal Detail:
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Title: Immunology letters Volume: 133 ISSN: 1879-0542 ISO Abbreviation: Immunol. Lett. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-27 Completed Date: 2011-05-16 Revised Date: 2011-10-31 |
Medline Journal Info:
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Nlm Unique ID: 7910006 Medline TA: Immunol Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 70-7 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibody Affinity Cells, Cultured Feedback, Physiological Immunoglobulin G / chemistry, metabolism* Interleukin-10 / secretion Interleukin-12 / secretion Macrophages / immunology, metabolism* Mice Mice, Inbred BALB C Phagocytosis* / immunology Protein Binding Receptor Aggregation / immunology Receptors, IgG / immunology, metabolism* Signal Transduction / immunology |
| Grant Support | |
ID/Acronym/Agency:
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AI 49383/AI/NIAID NIH HHS; R01 AI046805-04/AI/NIAID NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Immunoglobulin G; 0/Receptors, IgG; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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