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Slow release of soluble TNF receptors by monocytes in vitro
J F Leeuwenberg1, T M Jeunhomme, W A Buurman
1Department of Surgery, University of Limburg, Maastricht, The Netherlands.
Abstract:
In this study, we investigated the release of soluble(s) TNF-R by PBMC in vitro. T cell activation by mAb anti-CD3, as well as activation with phorbol esters (PMA), enhanced the release of both sTNF-R55 and sTNF-R75 by PBMC. In contrast to shedding of TNF-R by neutrophils upon activation, release of sTNF-R by PBMC proved to be a relatively slow process, reaching a plateau after 2 days of culture. Monocytes appeared to be the main source of the released sTNF-R, whereas activation of purified T cells induced only a minor release of sTNF-R as compared with the whole cell population. To unravel the mechanism, a number of cytokines were added during a 2-day culture of cells. IL-10 enhanced sTNF-R levels with similar kinetics as mAb anti-CD3 and PMA, whereas the other cytokines tested did not affect the release of sTNF-R by PBMC, pure T lymphocytes, or purified monocytes, either activated or not. Conversely, inhibitors of cytokines were added during the activation period to study the effect of endogenously produced cytokines on sTNF-R release. mAb anti-IL-10 and IL-1ra partly sTNF-R release, whereas other inhibitors did not affect the release. The results obtained in vitro may extend our insight in the mechanism via which sTNF-R are enhanced in vivo during inflammatory reactions.
Insights
Peripheral blood mononuclear cells (PBMC) release soluble tumor necrosis factor receptors (sTNF-R) upon activation. Interleukin-10 (IL-10) significantly enhances this release, suggesting a role in inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Soluble tumor necrosis factor receptors (sTNF-R) play a role in regulating TNF-alpha activity.
- Understanding the mechanisms of sTNF-R release is crucial for comprehending inflammatory processes.
Purpose of the Study:
- To investigate the release of sTNF-R by peripheral blood mononuclear cells (PBMC) in vitro.
- To identify factors and cellular sources involved in sTNF-R release.
Main Methods:
- PBMC were activated using monoclonal antibody anti-CD3 and phorbol esters (PMA).
- Cytokines (e.g., IL-10) and cytokine inhibitors (e.g., anti-IL-10, IL-1ra) were used to study their effects on sTNF-R release.
- Purified T cells and monocytes were cultured to determine the primary source of sTNF-R.
Main Results:
- Activation of PBMC with anti-CD3 or PMA enhanced the release of sTNF-R55 and sTNF-R75.
- Monocytes were identified as the main source of released sTNF-R.
- Interleukin-10 (IL-10) significantly enhanced sTNF-R release, while anti-IL-10 and IL-1ra partially inhibited it.
Conclusions:
- PBMC, particularly monocytes, release sTNF-R upon activation.
- IL-10 plays a key role in enhancing sTNF-R release from PBMC.
- These findings provide insights into sTNF-R regulation during inflammatory reactions.