A Critical Role for Syk in Signal Transduction and Phagocytosis Mediated by Fcγ Receptors on Macrophages
-
- Mary T. Crowley
- From the G.W. Hooper Foundation, *Department of Microbiology and Immunology, and ‡Department of Laboratory Medicine, University of California, San Francisco, California 94143-0552; and the §National Institute for Medical Research, London NW7 1AA, United Kingdom
-
- Patrick S. Costello
- From the G.W. Hooper Foundation, *Department of Microbiology and Immunology, and ‡Department of Laboratory Medicine, University of California, San Francisco, California 94143-0552; and the §National Institute for Medical Research, London NW7 1AA, United Kingdom
-
- Cheryl J. Fitzer-Attas
- From the G.W. Hooper Foundation, *Department of Microbiology and Immunology, and ‡Department of Laboratory Medicine, University of California, San Francisco, California 94143-0552; and the §National Institute for Medical Research, London NW7 1AA, United Kingdom
-
- Martin Turner
- From the G.W. Hooper Foundation, *Department of Microbiology and Immunology, and ‡Department of Laboratory Medicine, University of California, San Francisco, California 94143-0552; and the §National Institute for Medical Research, London NW7 1AA, United Kingdom
-
- Fanying Meng
- From the G.W. Hooper Foundation, *Department of Microbiology and Immunology, and ‡Department of Laboratory Medicine, University of California, San Francisco, California 94143-0552; and the §National Institute for Medical Research, London NW7 1AA, United Kingdom
-
- Clifford Lowell
- From the G.W. Hooper Foundation, *Department of Microbiology and Immunology, and ‡Department of Laboratory Medicine, University of California, San Francisco, California 94143-0552; and the §National Institute for Medical Research, London NW7 1AA, United Kingdom
-
- Victor L. J. Tybulewicz
- From the G.W. Hooper Foundation, *Department of Microbiology and Immunology, and ‡Department of Laboratory Medicine, University of California, San Francisco, California 94143-0552; and the §National Institute for Medical Research, London NW7 1AA, United Kingdom
-
- Anthony L. DeFranco
- From the G.W. Hooper Foundation, *Department of Microbiology and Immunology, and ‡Department of Laboratory Medicine, University of California, San Francisco, California 94143-0552; and the §National Institute for Medical Research, London NW7 1AA, United Kingdom
抄録
<jats:p>Receptors on macrophages for the Fc region of IgG (FcγR) mediate a number of responses important for host immunity. Signaling events necessary for these responses are likely initiated by the activation of Src-family and Syk-family tyrosine kinases after FcγR cross-linking. Macrophages derived from Syk-deficient (Syk−) mice were defective in phagocytosis of particles bound by FcγRs, as well as in many FcγR-induced signaling events, including tyrosine phosphorylation of a number of cellular substrates and activation of MAP kinases. In contrast, Syk− macrophages exhibited normal responses to another potent macrophage stimulus, lipopolysaccharide. Phagocytosis of latex beads and Escherichia coli bacteria was also not affected. Syk− macrophages exhibited formation of polymerized actin structures opposing particles bound to the cells by FcγRs (actin cups), but failed to proceed to internalization. Interestingly, inhibitors of phosphatidylinositol 3-kinase also blocked FcγR-mediated phagocytosis at this stage. Thus, PI 3-kinase may participate in a Syk-dependent signaling pathway critical for FcγR-mediated phagocytosis. Macrophages derived from mice deficient for the three members of the Src-family of kinases expressed in these cells, Hck, Fgr, and Lyn, exhibited poor Syk activation upon FcγR engagement, accompanied by a delay in FcγR-mediated phagocytosis. These observations demonstrate that Syk is critical for FcγR-mediated phagocytosis, as well as for signal transduction in macrophages. Additionally, our findings provide evidence to support a model of sequential tyrosine kinase activation by FcγR's analogous to models of signaling by the B and T cell antigen receptors.</jats:p>
収録刊行物
-
- The Journal of Experimental Medicine
-
The Journal of Experimental Medicine 186 (7), 1027-1039, 1997-10-06
Rockefeller University Press
- Tweet
詳細情報
-
- CRID
- 1360292620102727040
-
- NII論文ID
- 30017415963
-
- ISSN
- 15409538
- 00221007
-
- データソース種別
-
- Crossref
- CiNii Articles