Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn
Macrophage Fcγ receptors (FcγRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined FcγR signaling and phagocytic function in bone marrow–derived macrophages from mutant mice lacking the major Src family kinases expressed in these cells, Hck, Fgr, and...
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| Format: | Online |
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The Rockefeller University Press
2000
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195832/ |
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pubmed-21958322008-04-16 Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn Fitzer-Attas, Cheryl J. Lowry, Malcolm Crowley, Mary T. Finn, Alexander J. Meng, Fanying DeFranco, Anthony L. Lowell, Clifford A. Original Article Macrophage Fcγ receptors (FcγRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined FcγR signaling and phagocytic function in bone marrow–derived macrophages from mutant mice lacking the major Src family kinases expressed in these cells, Hck, Fgr, and Lyn. Many FcγR-induced functional responses and signaling events were diminished or delayed in these macrophages, including immunoglobulin (Ig)G-coated erythrocyte phagocytosis, respiratory burst, actin cup formation, and activation of Syk, phosphatidylinositol 3-kinase, and extracellular signal–regulated kinases 1 and 2. Significant reduction of IgG-dependent phagocytosis was not seen in hck − /−fgr − /− or lyn − /− cells, although the single mutant lyn − /− macrophages did manifest signaling defects. Thus, Src family kinases clearly have roles in two events leading to FcγR-mediated phagocytosis, one involving initiation of actin polymerization and the second involving activation of Syk and subsequent internalization. Since FcγR-mediated phagocytosis did occur at modest levels in a delayed fashion in triple mutant macrophages, these Src family kinases are not absolutely required for uptake of IgG-opsonized particles. The Rockefeller University Press 2000-02-21 /pmc/articles/PMC2195832/ /pubmed/10684859 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 |
Fitzer-Attas, Cheryl J. Lowry, Malcolm Crowley, Mary T. Finn, Alexander J. Meng, Fanying DeFranco, Anthony L. Lowell, Clifford A. |
| spellingShingle |
Fitzer-Attas, Cheryl J. Lowry, Malcolm Crowley, Mary T. Finn, Alexander J. Meng, Fanying DeFranco, Anthony L. Lowell, Clifford A. Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn |
| author_facet |
Fitzer-Attas, Cheryl J. Lowry, Malcolm Crowley, Mary T. Finn, Alexander J. Meng, Fanying DeFranco, Anthony L. Lowell, Clifford A. |
| author_sort |
Fitzer-Attas, Cheryl J. |
| title |
Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn |
| title_short |
Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn |
| title_full |
Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn |
| title_fullStr |
Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn |
| title_full_unstemmed |
Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn |
| title_sort |
fcγ receptor–mediated phagocytosis in macrophages lacking the src family tyrosine kinases hck, fgr, and lyn |
| description |
Macrophage Fcγ receptors (FcγRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined FcγR signaling and phagocytic function in bone marrow–derived macrophages from mutant mice lacking the major Src family kinases expressed in these cells, Hck, Fgr, and Lyn. Many FcγR-induced functional responses and signaling events were diminished or delayed in these macrophages, including immunoglobulin (Ig)G-coated erythrocyte phagocytosis, respiratory burst, actin cup formation, and activation of Syk, phosphatidylinositol 3-kinase, and extracellular signal–regulated kinases 1 and 2. Significant reduction of IgG-dependent phagocytosis was not seen in hck
−
/−fgr
−
/− or lyn
−
/− cells, although the single mutant lyn
−
/− macrophages did manifest signaling defects. Thus, Src family kinases clearly have roles in two events leading to FcγR-mediated phagocytosis, one involving initiation of actin polymerization and the second involving activation of Syk and subsequent internalization. Since FcγR-mediated phagocytosis did occur at modest levels in a delayed fashion in triple mutant macrophages, these Src family kinases are not absolutely required for uptake of IgG-opsonized particles. |
| publisher |
The Rockefeller University Press |
| publishDate |
2000 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195832/ |
| _version_ |
1611432282928709632 |