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Magnesium corrosion particles do not interfere with the immune function of primary human and murine macrophages.

ABSTRACT: Magnesium is currently under investigation as a prospective biodegradable implant material. Biodegradation of magnesium causes a release of magnesium, hydroxide ions and hydrogen gas but it can also lead to the formation of particulate debris. Implant-derived particles may have immunotoxic effects. To investigate the influence of magnesium-derived particles on the immune functions of primary macrophages, up to 500 μg/ml magnesium or magnesium corrosion particles were added to the cell culture medium. No major effects were observed on cell viability and on the release of the proinflammatory cytokine tumor necrosis factor (TNF)α. In addition, the ability of macrophages to stimulate proliferation of allogenic lymphocytes in a mixed leukocyte reaction remained unaffected. When macrophages were incubated with magnesium particles and then infected with the apathogenic Mycobacterium smegmatis, infection-induced TNFα secretion from murine macrophages was inhibited but not from human macrophages. However, the bactericidal activity of either cell type was not influenced. In conclusion, magnesium-related particles did not restrict the immune function of macrophages, suggesting that magnesium implants and corrosion particles derived thereof are highly biocompatible and have a low inflammatory potential.

SUBMITTER: Roth I

PROVIDER: S-EPMC5151114 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Magnesium corrosion particles do not interfere with the immune function of primary human and murine macrophages.

Roth Isabelle I Schumacher Stephan S Basler Tina T Baumert Kathrin K Seitz Jan-Marten JM Evertz Florian F Müller Peter Paul PP Bäumer Wolfgang W Kietzmann Manfred M

Progress in biomaterials 20141206 1

Magnesium is currently under investigation as a prospective biodegradable implant material. Biodegradation of magnesium causes a release of magnesium, hydroxide ions and hydrogen gas but it can also lead to the formation of particulate debris. Implant-derived particles may have immunotoxic effects. To investigate the influence of magnesium-derived particles on the immune functions of primary macrophages, up to 500 μg/ml magnesium or magnesium corrosion particles were added to the cell culture me ...[more]

PMID: 29470790

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Project description:BackgroundObesity promotes inflammation in adipose tissue (AT) and this is implicated in pathophysiological complications such as insulin resistance, type 2 diabetes and cardiovascular disease. Although based on the classical hypothesis, necrotic AT adipocytes (ATA) in obese state activate AT macrophages (ATM) that then lead to a sustained chronic inflammation in AT, the link between human adipocytes and the source of inflammation in AT has not been in-depth and systematically studied. So we decided as a new hypothesis to investigate human primary adipocytes alone to see whether they are able to prime inflammation in AT.Methods and resultsUsing mRNA expression, human preadipocytes and adipocytes express the cytokines/chemokines and their receptors, MHC II molecule genes and 14 acute phase reactants including C-reactive protein. Using multiplex ELISA revealed the expression of 50 cytokine/chemokine proteins by human adipocytes. Upon lipopolysaccharide stimulation, most of these adipocyte-associated cytokines/chemokines and immune cell modulating receptors were up-regulated and a few down-regulated such as (ICAM-1, VCAM-1, MCP-1, IP-10, IL-6, IL-8, TNF-α and TNF-β highly up-regulated and IL-2, IL-7, IL-10, IL-13 and VEGF down-regulated. In migration assay, human adipocyte-derived chemokines attracted significantly more CD4+ T cells than controls and the number of migrated CD4+ cells was doubled after treating the adipocytes with LPS. Neutralizing MCP-1 effect produced by adipocytes reduced CD4+ migration by approximately 30%.ConclusionHuman adipocytes express many cytokines/chemokines that are biologically functional. They are able to induce inflammation and activate CD4+ cells independent of macrophages. This suggests that the primary event in the sequence leading to chronic inflammation in AT is metabolic dysfunction in adipocytes, followed by production of immunological mediators by these adipocytes, which is then exacerbated by activated ATM, activation and recruitment of immune cells. This study provides novel knowledge about the prime of inflammation in human obese adipose tissue, opening a new avenue of investigations towards obesity-associated type 2 diabetes.

Project description:Aseptic loosening of total joint replacements is driven by a macrophage-mediated inflammatory reaction to implant-derived wear particles. Phagocytosis of implant debris has been suggested to activate the NLRP3 inflammasome leading to secretion of interleukin (IL)-1β. However, factors and molecular mechanisms driving the particle-induced inflammasome activation are yet to be fully elucidated. In this study, we investigated the inflammasome response of human primary macrophages to titanium, chromium, and molybdenum particles in vitro. We observed that particles alone were not sufficient to induce IL-1β secretion, but an additional priming signal-such as bacterial lipopolysaccharide (LPS)-was required to license the inflammasome activation. By using specific inhibitors against the inflammasome signaling pathway, we demonstrate that the particle-induced IL-1β secretion depended upon activation of the NLRP3 inflammasome. We further hypothesized that tumor necrosis factor (TNF) could substitute for LPS as a priming signal, and found that particle stimulation together with preceding TNF treatment resulted in inflammasome-dependent IL-1β production as well. Our results show that the NLRP3 inflammasome mediates wear particle responses in human primary macrophages, and its activation does not necessarily require the presence of bacterial components, but can be induced under aseptic conditions by TNF priming. STATEMENT OF SIGNIFICANCE: This study was conducted to elucidate the molecular mechanisms of metal particle-induced IL-1β secretion in human primary macrophages. Production of this pro-inflammatory mediator from wear particle-activated macrophages has been associated with increased bone loss around total joint replacements-a condition eventually requiring revision surgery. Our results confirm that together with a co-stimulatory priming signal, particles of common implant metals elicit macrophage-mediated IL-1β secretion through activation of the NLRP3 inflammasome pathway. We also present a concept of TNF priming in this context, demonstrating that the particle-related IL-1β secretion can take place in a truly sterile environment. Thus, inhibition of inflammasome signaling appears a means to prevent wear particle-induced inflammation and development of peri‑prosthetic osteolysis.

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Magnesium corrosion particles do not interfere with the immune function of primary human and murine macrophages.

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Magnesium corrosion particles do not interfere with the immune function of primary human and murine macrophages.

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