Spermine inhibition of monocyte activation and inflammation
Open accessAbstract
The innate immune system functions as a defensive front line against pathogenic invasion, but the proinflammatory products of activated monocytes and macrophages (e.g., TNF and NO) can also injure normal cells. Anti-inflammatory mediators restrain the innate immune response and prevent excessive collateral tissue damage. Spermine, a ubiquitous biogenic polyamine, specifically and reversibly suppresses the synthesis of monocyte proinflammatory cytokines. This may provide a counterregulatory mechanism to restrain monocyte activation in injured or infected tissues and in tumors where spermine levels are significantly increased. Here we show that monocyte spermine uptake was significantly increased following lipopolysaccharide stimulation. The polyamine analogue 1, 4-bis(3-aminopropyl)-piperazine (BAP) inhibited LPS-stimulated monocyte spermine uptake via the "nonselective" polyamine transporter. BAP fully restored macrophage TNF synthesis despite the presence of spermine, indicating that the mechanism of monocyte deactivation by spermine is dependent on spermine uptake. Administration of BAP in vivo significantly augmented the development of carrageenan-induced paw edema and nitric oxide release. Thus, endogenous spermine normally inhibits the innate inflammatory response by restraining macrophages.
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Extraneous spermine is taken up by monocytes and macrophages and selectively inhibits LPS-induced expression of pro-inflammatory cytokines.
“Extraneous spermine is taken up by monocytes and macrophages and selectively inhibits the LPS-induced expression of pro-inflammatory cytokines (M. Zhang et al., 1999; 1997).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as M. Zhang et al., 1999
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- Authors
- Zhang, M., Borovikova, L. V., Wang, H., Metz, C., & Tracey, K. J.
- Affiliations
- North Shore University Hospital (US)
- Corresponding author
- Zhang, Minghuang
- Venue
- Molecular Medicine
- Published
- 1999-09
- Volume
- 5
- Issue
- 9
- Pages
- 595-605
- ISSN
- 1076-1551 (ISSN-L)
- 1528-3658
- PMC
- PMC2230461
- OpenAlex
- W209376982
- Cited by
- 92
- References
- 38
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 7 · 2016: 3 · 2015: 1 · 2014: 4 · 2013: 5 · 2012: 4
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- spermine, monocyte activation, inflammation, innate immunity, polyamines, polyamine uptake, BAP, lipopolysaccharide, macrophages, nitric oxide, carrageenan-induced paw edema, anti-inflammatory regulation
- MeSH terms
- Animals, Carrageenan, Edema, Humans, Inflammation, Lipopolysaccharides, Macrophage Activation, Male, Monocytes, Piperazines, Polyamines, Rats, Inbred Lew, Spermine, Rats
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