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PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner
Abstract
We recently reported that intravenous injections of "empty" PEGylated liposomes without encapsulated or surface coupled proteins elicit a PEG-specific IgM response in rats. In the present study, simultaneous weak anti-PEG IgG and strong anti-PEG IgM responses were detected following intravenous injections of "empty" PEGylated liposomes. The pattern of immune response appears to differ from the classic primary response against T cell-dependent (TD) antigens. The anti-PEG IgM response was detected in T-cell deficient nude BALB/c mice following intravenous injection of "empty" PEGylated liposomes, suggesting that "empty" PEGylated liposomes initiate the immune response against PEG in a T cell-independent manner. In vitro splenic lymphocytes-proliferation assay indicated that TNP-LPS, a typical type 1 T cell-independent (TI) antigen (TI-1 antigen), significantly primed the proliferation, while TNP-Ficoll, a typical type 2 TI antigen (TI-2 antigen), and "empty" PEGylated liposomes did not prime any proliferation under these experimental conditions. In addition, in splenic marginal zone (MZ) B-cell-depleted rats, the anti-PEG IgM response was diminished, while the immune reactions against TNP-BSA (a TD antigen) and TNP-LPS (TI-1 antigen) were not diminished. These results demonstrate that "empty" PEGylated liposomes may promote the immune response against PEG as a result of priming the activation of MZ B cells, as TI-2 antigen promotes a specific IgM response. In conclusion, although the mechanistic details behind the immune reaction against "empty" PEGylated liposomes are not yet clear, the liposomes elicit an anti-PEG IgM response in a T cell-independent manner and appear to be a TI-2 antigen, and splenic MZ B cells may be essential for the immune response against "empty" PEGylated liposomes.
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“However, some reports also demonstrated the generation of PEG-specific antibodies after administration of PEG-coated liposomes [153, 154].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [153]
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Metadata
- Authors
- Ishida, T., Wang, X., Shimizu, T., Nawata, K., & Kiwada, H.
- Affiliations
- Tokushima University (JP)
- Corresponding author
- Kiwada, Hiroshi
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 122
- Issue
- 3
- Pages
- 349-355
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2087167636
- Cited by
- 382
- References
- 45
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 14 · 2023: 28 · 2022: 20 · 2021: 23 · 2020: 25 · 2019: 13 · 2018: 32 · 2017: 22 · 2016: 24 · 2015: 29 · 2014: 24 · 2013: 29 · 2012: 25
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kao Foundation for Arts and Sciences
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- PEGylated liposomes, T cell-independent immunity, marginal zone B cells, nude mice, TNP-LPS, TNP-Ficoll, splenocyte proliferation, intravenous injection
- MeSH terms
- Animals, Antigens, T-Independent, Cyclophosphamide, Immunoglobulin G, Immunoglobulin M, Injections, Intravenous, Liposomes, Male, Mice, Inbred BALB C, Mice, Nude, Polyethylene Glycols, Spleen, T-Lymphocytes, Rats, Wistar, Cell Proliferation, Mice, Rats
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