title: Slow release of soluble TNF receptors by monocytes in vitro.
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.
authors.affiliation: Department of Surgery, University of Limburg, Maastricht, The Netherlands.
authors.forename: J F
authors.initials: JF
authors.lastname: Leeuwenberg
authors.forename: T M
authors.initials: TM
authors.lastname: Jeunhomme
authors.forename: W A
authors.initials: WA
authors.lastname: Buurman
mesh_terms: D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000737:chemistry / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor