Neha Mishra, Magdalena Mohs, Nico Wittmann, Stefan Gross, Paul R. Thompson, Lukas Bossaller
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引用次数: 0
Abstract
Macrophages can respond to infection or cellular stress by forming inflammasomes or by releasing extracellular traps (ETs) of DNA through METosis. While ETs have been extensively studied in neutrophils, there are fewer studies on METosis. We show that extracellular calcium and LPS enable human monocyte-derived macrophages (hMDM) to release extracellular DNA decorated with myeloperoxidase (MPO) and citrullinated histone, alongside ASC aggregation and IL-1ß maturation, indicating NLRP3 inflammasome activation. Compared with m-CSF differentiated macrophages only gm-CSF differentiated macrophages expressed macrophage elastase (MMP12) and METs released by the latter had significantly more bactericidal activity toward E. coli. Mechanistically, phospholipase C and peptidyl arginine deiminase-2 inhibition attenuate MET release. Interestingly, NLRP3 inflammasome blockade by MCC950 had a significant effect on MET release. Finally, MET release was completely blocked by plasma membrane stabilization by punicalagin. Altogether, we demonstrate that extracellular calcium-activated hMDM extrude DNA, containing citrullinated histones, MPO, MMP12, and ASC specks and released METs kill bacteria independent of hMDM phagocytotic activity. We believe that calcium-activated hMDM adds a physiologically relevant condition to calcium ionophore induced cell death that may be important in autoimmunity.
期刊介绍:
The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.