The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Internalization and degradation of macrophage Fc receptors bound to polyvalent immune complexes.
Open accessAbstract
We have studied the Fc receptor-mediated pinocytosis of immunoglobulin G (IgG)-containing immune complexes by mouse macrophages. IgG complexes were formed from affinity-purified rabbit dinitrophenyl IgG and dinitrophenyl modified BSA at molar ratios of 2.5-10:1. Both the specificity of binding and the fate of internalized receptors were analyzed using monoclonal and polyclonal anti-Fc receptor antibodies. Based on the susceptibility of surface-bound ligand to release by proteolysis, we have found that at 37 degrees C, 125I-labeled IgG complexes were rapidly internalized (t1/2 less than 2 min) and delivered to lysosomes; acid-soluble 125I was detectable in the growth medium within 5-10 min of uptake. However, kinetic evidence indicated that Fc receptors were not efficiently re-used for multiple rounds of ligand uptake. Instead, macrophages that were exposed continuously to saturating concentrations of IgG complexes exhibited a selective and largely irreversible removal of Fc receptors from the plasma membrane. This loss of surface receptors correlated with an increased rate of receptor turnover, determined by immune precipitation of Fc receptors from 125I-labeled macrophages. Thus, in contrast to the results obtained in the accompanying paper (I. Mellman, H. Plutner, and P. Ukkonen, 1984, J. Cell Biol. 98:1163-1169) using a monovalent ligand, these data indicate that the interaction of Fc receptors with polyvalent complexes leads to the degradation of both ligand and receptor following their delivery to lysosomes.
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“Target‐mediated clearance refers to the elimination of mAbs through its antigen‐specific interactions. After mAbs bind to a specific antigen (soluble or membrane bound) they may be internalized and catabolized through lysosomal degradation as an antibody–antigen complex.35”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [35]
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Cites
Fraker, P. J., & Speck, J. C. (1978) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(78)91322-0 · Cited by 4,553
Coated pits, coated vesicles, and receptor-mediated endocytosis
Goldstein, J. L., Anderson, R. G. W., & Brown, M. S. (1979) · Nature · doi:10.1038/279679a0 · Cited by 1,532
Endocytosis and the recycling of plasma membrane.
Steinman, R. M., Mellman, I., Müller, W. A., & Cohn, Z. A. (1983) · The Journal of Cell Biology · doi:10.1083/jcb.96.1.1 · Cited by 1,459
Self-citationCarpenter, G., & Cohen, S. (1976) · The Journal of Cell Biology · doi:10.1083/jcb.71.1.159 · Cited by 1,291
Unkeless, J. C. (1979) · The Journal of Experimental Medicine · doi:10.1084/jem.150.3.580 · Cited by 1,271
Binding and Degradation of Low Density Lipoproteins by Cultured Human Fibroblasts
Goldstein, J. L., & Brown, M. S. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42341-7 · Cited by 1,123
Gavin, J. R., Roth, J., Neville, D. M., MEYTS, P. D., & Buell, D. N. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.1.84 · Cited by 1,040
González‐Noriega, A., Grubb, J. H., Talkad, V. D., & Sly, W. S. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.85.3.839 · Cited by 736
THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES
Cohn, Z. A., & Benson, B. (1965) · The Journal of Experimental Medicine · doi:10.1084/jem.121.1.153 · Cited by 691
Rapid acidification of endocytic vesicles containing α2-macroglobulin
Tycko, B., & Maxfield, F. R. (1982) · Cell · doi:10.1016/0092-8674(82)90219-7 · Cited by 673
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ENDOCYTOSIS AND MOLECULAR SORTING
Mellman, I. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.575 · Cited by 1,551
Self-citationCAPTURE AND PROCESSING OF EXOGENOUS ANTIGENS FOR PRESENTATION ON MHC MOLECULES
Watts, C. K. W. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.821 · Cited by 754
Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies
Keizer, R. J., Huitema, A. D. R., Schellens, J. H. M., & Beijnen, J. H. (2010) · Clinical Pharmacokinetics · doi:10.2165/11531280-000000000-00000 · Cited by 725
Membrane transport in the endocytic pathway
Grüenberg, J., & Maxfield, F. R. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80013-1 · Cited by 645
Wileman, T. E., Harding, C., & Stahl, P. D. (1985) · Biochemical Journal · doi:10.1042/bj2320001 · Cited by 566
Metadata
- Authors
- Mellman, I., & Plutner, H.
- ORCID
- Mellman, I
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1984-04-01
- Volume
- 98
- Issue
- 4
- Pages
- 1170-1177
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2113248
- OpenAlex
- W2075507579
- Cited by
- 251
- References
- 34
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 4 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 21.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- Fc receptors, macrophages, immune complexes, receptor internalization, receptor degradation, pinocytosis, lysosomes, receptor turnover, IgG, ligand uptake, receptor recycling
- MeSH terms
- Animals, Antibodies, Monoclonal, Antigen-Antibody Complex, Cell Line, Immunoglobulin G, Kinetics, Macrophages, Microscopy, Fluorescence, Pinocytosis, Receptors, Fc, Mice
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