The Energy-dependent Hierarchy of Immune Functions in Human Monocytes

Pierre-Louis Krauß¹, Thomas Buttgereit², Yuling Chen¹, Moritz Pfeiffenberger¹, Timo Gaber¹ and Frank Buttgereit³, ¹Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Berlin, Germany, ²Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Dermatology, Venerology, and Allergology, Berlin, Germany, ³Charité University Medicine, Berlin, Germany

Meeting: ACR Convergence 2020

Keywords: cytokines, Inflammation, Monocytes/macrophages

Session Information

Date: Friday, November 6, 2020

Session Title: Innate Immunity Poster

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: At sites of inflammation, monocytes carry out specific immunological functions while facing challenging bioenergetic restrictions. Here, we investigated the potential of human monocytes to adapt under conditions of reduced energy supply by gradually inhibiting oxidative phosphorylation (OXPHOS) under glucose free conditions.

Methods: We modelled this reduced energy supply with myxothiazol, an inhibitor of mitochondrial respiration, at 0, 2 and 4 pmol/10⁶ cells to decrease mitochondrial ATP production for 0%, 25% and 66% under glucose free conditions. For the three energy levels, we assessed (i) phagocytosis of FITC-labelled E.coli using flow cytometry, (i) production of reactive oxygen species (ROS) through NADPH oxidase (NOX) as determined by VAS2870-sensitive OCR using a Clark-type electrode, (iii) ATP generation and steady state level using a Clark-type electrode and luminometric assessment (iv) expression of surface activation markers CD16, CD80, CD11b, HLA-DR and (v) production of the inflammatory cytokines IL-1β, IL-6 and TNF-α using flow cytometry in peripheral blood-derived human monocytes with and without LPS-stimulation.

Results: As a prerequisite for our study, we demonstrate that human monocytes survived strong inhibition of mitochondrial respiration without any sign of apoptosis as determined by flow cytometry. As a result of the inhibition of OXPHOS, we demonstrate a reduction of VAS2870-sensitive OCR (ROS production through NOX), ATPase-dependent OCR and ATP steady-state levels. Focusing on immune function, we observed that phagocytosis and the production of IL-6 were the least sensitive to reduced energy supply while surface expression of CD11b, HLA-DR, production of TNF-α and IL-1β were most affected by inhibition of OXPHOS.

Conclusion: Our data demonstrate an energy-dependent hierarchy of immune functions in monocytes, which may represent a potential therapeutic target in monocyte-mediated inflammatory diseases.

Disclosure: P. Krauß, None; T. Buttgereit, None; Y. Chen, None; M. Pfeiffenberger, None; T. Gaber, None; F. Buttgereit, AbbVie, 8, Eli Lilly, 8, Pfizer, 8, Roche, 8.

To cite this abstract in AMA style:

Krauß P, Buttgereit T, Chen Y, Pfeiffenberger M, Gaber T, Buttgereit F. The Energy-dependent Hierarchy of Immune Functions in Human Monocytes [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/the-energy-dependent-hierarchy-of-immune-functions-in-human-monocytes/. Accessed January 19, 2021.

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