Fig 1: Correlations between myeloperoxidase (MPO) levels, MPO activity and soluble glycocalyx proteins at acute and convalescent phases.Non-severe (n = 15), severe (n = 10) and pre-COVID-19. A Acute (syndecan-1 vs MPO levels); B Convalescent (syndecan-1 vs MPO levels); C Acute (syndecan-1 vs MPO activity); D Convalescent (syndecan-1 vs MPO activity); E Acute (glypican-1 vs MPO levels); F Convalescent (glypican-1 vs MPO levels); G Acute (glypican-1 vs MPO activity); H Convalescent (glypican-1 vs MPO activity). Rho and P value determined by spearman correlation tests.
Fig 2: Blood concentrations of myeloperoxidase (MPO), MPO activity, syndecan-1 and glypican-1 in COVID-19 subjects at acute and convalescent phases, and controls.Non-severe (n = 15), severe (n = 10) and pre-COVID-19 controls (n = 9). A MPO concentrations; B MPO activity; C Syndecan-1 concentrations; D Glypican-1 concentrations. Data presented in box and whiskers plots demonstrating median and interquartile range, and whiskers representing 10-90 percentiles. A, C, D Protein concentrations were extrapolated from serially diluted standard curves presented in ng/ml. MPO activity: amount of MPO required to generate taurine choloramine to consume 1.0 μmol of DTNB probe per minute at room temperature (incubated for 60 min) presented in unit/ml. Solid lines across groups; bars between groups. *P < 0.05, **P < 0.01, ***P < 0.001 by the Kruskal–Wallis test and Wilcoxon sign rank test.
Fig 3: Convalescent COVID-19 plasma induced endothelial glycocalyx shedding and myeloperoxidase (MPO) inhibition reduced shedding.A, B Graphical representative of cleaved syndecan-1 and glypican-1 (ng/ml) from human aortic endothelial cells treated with convalescent COVID-19 plasma [uncomplicated (n = 5) and complicated (n = 5)], control plasma (n = 3)], purified MPO (50 μM) with hydrogen peroxide (30 μM), in the presence or absence of an irreversible MPO-inhibitors (MPO-inhibitor-28, 10 μM and AZD-5904, 10 μM), after 16 h. Data are representative of two independent experiments. Middle solid lines are mean ± SD. Protein concentrations were extrapolated from serially diluted standard curves. Solid lines: measurements across groups; bars: measurements between groups. *P < 0.05, **P < 0.01 by paired-t test. Individual samples were randomly picked. Note, only 4 samples from uncomplicated group were available for MPO inhibition with AZD5904. Untreated convalescent plasma syndecan-1 levels [mean (SD); non-severe 0.35 (0.55) ng/ml; severe 2.34 (1.39) ng/ml].
Fig 4: Plasma myeloperoxidase (MPO) activity and treatment with MPO inhibitors.Data generated with COVID-19 recovery samples comprising of severe COVID-19 (n = 5), non-severe (n = 5); and controls (n = 3). Plasma MPO activity was determined in untreated or treated with MPO-inhibitors (MPO-inhibitor-28, 10 μM and AZD-5904, 10 μM). ****P < 0.001 by paired-t test. Data presented in scatter plot, horizontal lines represent mean and ±(S.E.M).
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