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. 2021 Jul 9;129(4):e54–e71. doi: 10.1161/CIRCRESAHA.121.319142

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© 2021 American Heart Association, Inc.

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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Figure 7. — Regulation of coronavirus disease 2019 (COVID-19) patient monocyte-derived macrophage phenotype and function by specialized proresolving mediator (SPM). A–F, Monocytes were isolated from peripheral blood of patients with COVID-19 and differentiated to monocyte-derived macrophages with GM-CSF in the presence of vehicle or 10 nmol/L of the indicated SPM. On day 7, (A) cells were lifted and the expression of the indicated phenotypic markers was assessed using flow cytometry (n=13 patients with COVID-19) or (B–F) cells were incubated with recombinant human S100A8/A9 dimer (1 µg/mL, 24 h) and Brefeldin A (2 µg/mL, for final 18 h) and the expression of indicated cytokines was assessed using flow cytometry (n=12 patients with COVID-19). Results are reported as percentage change in expression from levels in cells incubated with vehicle only. Statistical differences between vehicle and SPM treatments were established using Kruskal-Wallis test with Dunn post hoc correction. G–I, Monocytes from patients with COVID-19 were differentiated to monocyte-derived macrophages with GM-CSF, incubated with the indicated SPM (0.1 or 1 nmol/L) or vehicle for 15 min followed by fluorescently labeled (G) S. aureus, (H) S. pneumoniae, (I) zymosan, or (J) apoptotic cells. Results are reported as percentage change in uptake from levels in cells incubated with vehicle only. For (G–H), n=16 (for 0.1 nmol/L SPM) and n=15 (for 1 nmol/L SPM) patients with COVID-19. For (I), n=12 (for 0.1 nmol/L SPM) and n=11 (for 1 nmol/L SPM) patients with COVID-19. For (J), n=14 (for 0.1 nmol/L SPM) and n=8 (for 1 nmol/L SPM) patients with COVID-19. Statistical differences between SPM treatments and vehicle were established using Wilcoxon Signed Rank test for each mediator and raw P values are displayed. IL indicates interleukin; MCTR indicates maresin conjugates in tissue regeneration; PCTR, protectin conjugates in tissue regeneration; RvD, D-series resolvin; and TNF, tumor necrosis factor.