Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr
Ingestion of opsonized pathogens by professional phagocytes results in the generation and release of microbicidal products that are essential for normal host defense. Because these products can result in significant tissue injury, phagocytosis must be regulated to limit damage to the host while allo...
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| Format: | Online |
| Language: | English |
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The Rockefeller University Press
2000
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195814/ |
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pubmed-2195814 |
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pubmed-21958142008-04-16 Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr Gresham, Hattie D. Dale, Benjamin M. Potter, Jeffrey W. Chang, Peter W. Vines, Charlotte M. Lowell, Clifford A. Lagenaur, Carl F. Willman, Cheryl L. Original Article Ingestion of opsonized pathogens by professional phagocytes results in the generation and release of microbicidal products that are essential for normal host defense. Because these products can result in significant tissue injury, phagocytosis must be regulated to limit damage to the host while allowing for optimal clearance and destruction of opsonized pathogens. To pursue negative regulation of phagocytosis, we assessed the effect of the Src kinase family member, Fgr, on opsonin-dependent phagocytosis by mouse macrophages. We chose Fgr because it is present in high concentrations in circulating phagocytes but is not essential for Fcγ receptor–mediated ingestion by mouse macrophages. Although expression of Fgr both in a macrophage cell line and in primary macrophages significantly attenuates ingestion mediated by Fcγ receptors and CR3, it does not affect macropinocytosis or receptor-mediated endocytosis. This selective effect of Fgr is independent of its tyrosine kinase function. After Fcγ receptor cross-linking, Fgr becomes associated with the immunoreceptor tyrosine-based inhibition motif (ITIM)–containing receptor, SIRPα (a member of the signal-regulatory protein family, also known as Src homology 2 domain–containing protein tyrosine phosphatase [SHP] substrate 1 [SHPS-1], brain immunoglobulin-like molecule with tyrosine-based activation motifs [BIT], and P84) and potentiates the association of the phosphatase SHP-1 with SIRPα. This association is responsible, at least in part, for decreasing positive signaling essential for optimal phagocytosis. These data demonstrate an important negative regulatory role for this Src kinase family member and suggest that this homeostatic function must be overcome for optimal uptake and clearance of opsonized pathogens. The Rockefeller University Press 2000-02-07 /pmc/articles/PMC2195814/ /pubmed/10662797 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Gresham, Hattie D. Dale, Benjamin M. Potter, Jeffrey W. Chang, Peter W. Vines, Charlotte M. Lowell, Clifford A. Lagenaur, Carl F. Willman, Cheryl L. |
| spellingShingle |
Gresham, Hattie D. Dale, Benjamin M. Potter, Jeffrey W. Chang, Peter W. Vines, Charlotte M. Lowell, Clifford A. Lagenaur, Carl F. Willman, Cheryl L. Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr |
| author_facet |
Gresham, Hattie D. Dale, Benjamin M. Potter, Jeffrey W. Chang, Peter W. Vines, Charlotte M. Lowell, Clifford A. Lagenaur, Carl F. Willman, Cheryl L. |
| author_sort |
Gresham, Hattie D. |
| title |
Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr |
| title_short |
Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr |
| title_full |
Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr |
| title_fullStr |
Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr |
| title_full_unstemmed |
Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr |
| title_sort |
negative regulation of phagocytosis in murine macrophages by the src kinase family member, fgr |
| description |
Ingestion of opsonized pathogens by professional phagocytes results in the generation and release of microbicidal products that are essential for normal host defense. Because these products can result in significant tissue injury, phagocytosis must be regulated to limit damage to the host while allowing for optimal clearance and destruction of opsonized pathogens. To pursue negative regulation of phagocytosis, we assessed the effect of the Src kinase family member, Fgr, on opsonin-dependent phagocytosis by mouse macrophages. We chose Fgr because it is present in high concentrations in circulating phagocytes but is not essential for Fcγ receptor–mediated ingestion by mouse macrophages. Although expression of Fgr both in a macrophage cell line and in primary macrophages significantly attenuates ingestion mediated by Fcγ receptors and CR3, it does not affect macropinocytosis or receptor-mediated endocytosis. This selective effect of Fgr is independent of its tyrosine kinase function. After Fcγ receptor cross-linking, Fgr becomes associated with the immunoreceptor tyrosine-based inhibition motif (ITIM)–containing receptor, SIRPα (a member of the signal-regulatory protein family, also known as Src homology 2 domain–containing protein tyrosine phosphatase [SHP] substrate 1 [SHPS-1], brain immunoglobulin-like molecule with tyrosine-based activation motifs [BIT], and P84) and potentiates the association of the phosphatase SHP-1 with SIRPα. This association is responsible, at least in part, for decreasing positive signaling essential for optimal phagocytosis. These data demonstrate an important negative regulatory role for this Src kinase family member and suggest that this homeostatic function must be overcome for optimal uptake and clearance of opsonized pathogens. |
| publisher |
The Rockefeller University Press |
| publishDate |
2000 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195814/ |
| _version_ |
1611432271345090560 |