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Enhancement of mixed leukocyte reaction and cytotoxic antitumor responses by heparin
Abstract
The immunomodulating effects of heparin and natural and synthetic heparinoids (which are now undergoing clinical trials for the treatment of AIDS) on cellular immunity (DNA synthesis and cytotoxic responses of mouse lymphocytes to allogeneic cells and histocompatible tumors) were studied. The results showed that (1) high and low m.w. heparin enhanced mouse antitumor and antiallogeneic cell responses in vitro; (2) other sulfated heparinoids did not have this enhancing activity and some of them (including dextran sulfate) totally suppressed generation of cytotoxic cells; (3) these immunomodulating activities of heparin and heparinoids did not correlate with their anticoagulant effects, degree of sulfation, and mitogenic activity; (4) heparin did not increase the production of IL-2 and did not enhance the action of IL-2 on the cells in MLC, heparin also had no effect on the growth-promoting activity of IL-2 on cloned cytotoxic T cells; (5) heparin had a synergistic enhancing effect with IL-1 on the generation of cytotoxic cells in MLC; and (6) heparin abolished endothelial cell growth factor-induced suppression of cytotoxic response. The latter two effects by themselves, however, could not fully explain the entire immunoenhancing activity of heparin. These results indicate that heparin and heparinoids have multiple effects on the immune system and that some of them can enhance, whereas others can suppress cell-mediated responses.
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Activation of the innate immune system by polysaccharides leads to attraction of macrophages and natural killer cells to the target site and production of tumoricidal cytokines.
“The main mechanism of action of polysaccharides cytotoxic effect is the activation of the innate immune system [165,166,167,168], leading to attraction of macrophages and natural killer cells to the target site and production of tumoricidal cytokines [166,169,170,171].”
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Metadata
- Authors
- Dziarski, R.
- Affiliations
- Indiana University School of Medicine (US)
- Corresponding author
- Dziarski, R
- ORCID
- Dziarski, R
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1989-07-01
- Volume
- 143
- Issue
- 1
- Pages
- 356-365
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1608838015
- Cited by
- 26
- References
- 0
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2019: 4
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 36640)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- heparin, heparinoids, mixed lymphocyte reaction, cytotoxic T lymphocytes, antitumor immunity, immunomodulation, interleukin-1, interleukin-2, dextran sulfate, endothelial cell growth factor, cell-mediated immunity, sulfated polysaccharides
- MeSH terms
- Adjuvants, Immunologic, Animals, Blood Coagulation, Cytotoxicity, Immunologic, Female, Growth Substances, Heparin, Heparinoids, Interleukin-1, Interleukin-2, Lymphocyte Culture Test, Mixed, Lymphocyte Activation, Male, Mice, Inbred BALB C, Mice, Inbred CBA, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Mitogens, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured, Endothelial Growth Factors, Mice
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