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Systemic inflammation induces release of cell-free DNA from hematopoietic and parenchymal cells in mice and humans by Anne Jan van der Meer, Anna Kroeze,

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Presentation on theme: "Systemic inflammation induces release of cell-free DNA from hematopoietic and parenchymal cells in mice and humans by Anne Jan van der Meer, Anna Kroeze,"— Presentation transcript:

1 Systemic inflammation induces release of cell-free DNA from hematopoietic and parenchymal cells in mice and humans by Anne Jan van der Meer, Anna Kroeze, Arie J. Hoogendijk, Aicha Ait Soussan, C. Ellen van der Schoot, Walter A. Wuillemin, Carlijn Voermans, Tom van der Poll, and Sacha Zeerleder BloodAdv Volume 3(5): March 12, 2019 © 2019 by The American Society of Hematology

2 Nucleosomes have other origins besides neutrophils.
Nucleosomes have other origins besides neutrophils. (A) Nucleosomes and EA complex levels in plasma of humans injected with LPS at t = 0 (n = 8). (B) Nucleosome levels positively correlate to EA complex levels in LPS-challenged subjects. (C) Nucleosome levels in septic patients with neutrophil activation on admission (>100 ng/mL, n = 8) or without neutrophil activation (<100 ng/mL, n = 12) are not statistically different. (D) Nucleosomes and EA complex levels in plasma of sepsis patients (n = 20) at start of admission and during admission to the hospital. (E) No correlation exists between nucleosome and EA complex levels in the previously mentioned sepsis patients. Data are represented as mean ± standard error (A,D) or median ± interquartile range (C). P < .05 was considered significant. ns, not significant. Anne Jan van der Meer et al. Blood Adv 2019;3: © 2019 by The American Society of Hematology

3 Upon LPS challenge in mice, nucleosomes are derived from both hematopoietic and nonhematopoietic cells. Upon LPS challenge in mice, nucleosomes are derived from both hematopoietic and nonhematopoietic cells. Plasma nucleosomes (A) and MPO (B) levels after intraperitoneal injection of LPS in mice; n = 8 per group. (C) The ratio of nucleosomes vs MPO in LPS-challenged mice. (D) Model of male/female mixed bone marrow chimera mice. General IL-3 gene PCR (E) and specific SRY PCR (F) on extracellular DNA before and 6 and 20 hours after LPS challenge in male/female mixed chimera mice. Pre-LPS (●), n = 1-2 per group; 6 hours after LPS (▪), n = 4-7; and 20 hours after LPS (▲), n = 5-7. Data are presented as mean ± standard error. P < .05 was considered significant. *P < .05, **P < .01, ***P < .001, ****P < Anne Jan van der Meer et al. Blood Adv 2019;3: © 2019 by The American Society of Hematology

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