The effect of anoxia on functions of neonatal monocytes and neutrophils

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Dokumentart: PhDThesis
Date: 2021-12-21
Language: English
Faculty: 4 Medizinische Fakultät
Department: Medizin
Advisor: Gille, Christian (PD Dr.)
Day of Oral Examination: 2021-12-13
DDC Classifikation: 610 - Medicine and health
Keywords: Anoxie , Monozyt , Neutrophiler Granulozyt
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The effect of anoxia on functions of neonatal monocytes and neutrophils Background and hypothesis: Neonatal sepsis is a major cause of neonatal morbidity and mortality. The consequences of neonatal sepsis are severe; in addition to high mortality rates, neonatal sepsis increases the risk of post-inflammatory secondary diseases such as bronchopulmonary dysplasia (BPD) and periventricular leucomalacia (PVL). A functional "immaturity" of the neonatal immune system compared to the adult immune system may explain the increased risk for generalization of infections. In adult immune cells, hypoxia is an important activator of inflammatory responses. The fetus develops in a hypoxic environment. However, little is known about the impact of hypoxia on neonatal immune functions. The aim of the present study was to investigate the effect of anoxia on functions of neonatal monocytes and neutrophils in comparison to adult monocytes and neutrophils with the hypothesis that anoxia stimulates inflammatory immune functions in adult but not in cord blood cells. Methods: Neonatal and adult cells were incubated for four hours under normoxia or anoxia. Phagocytic activity, expression of phagocytosis receptors CD11b and CD18, production of ROS and apoptosis rates and cytokine production was analyzed by flow cytometry. Net formation was investigated by confocal microscopy and the expression of HIF-1α protein was assessed by western blot. Results: Anoxia led to a significant increase in phagocytosis rates and ROS-production in adult monocytes but not cord blood monocytes and to a downregulation of CD11b and CD18 expression in cord blood but not adult monocytes. In neutrophils, the phagocytosis rate did not change upon anoxia, neither in cord blood nor in adult cells, whereas anoxia upregulated CD11b and CD18 expression in adult neutrophils but not in cord blood neutrophils. Unlike in monocytes, anoxia downregulated ROS production and increased apoptosis in both adult and cord blood cells. Expression of the cytokine IL-6 was upregulated by anoxia in adult neutrophils, while no change was observed in cord blood neutrophils. No effect of anoxia was observed on IL-8 expression. Both adult and cord blood neutrophils were able to form NETS upon stimulation with PMA, but anoxia did not lead to NETosis in both cell types. Finally, No HIF-1α expression was found neither in adult nor in cord blood neutrophils after culture in anoxia. Conclusion: It might be due to different HIF-1α protein expression, anoxia increases phagocytosis rate, ROS production and CD11b and CD18 expression in adult peripheral blood monocytes but not in cord blood monocytes. For neutrophils, anoxia stimulates CD11b and CD18 and IL-6 expression in adult peripheral blood but not in cord blood whereas phagocytosis rates, production of IL-8 and NETosis did not differ between PB neutrophils or CB neutrophils under normoxia or anoxia. HIF-1α could not be detected in adult and cord blood PMNs. Taken together, anoxia seems to stimulate inflammatory response of adult innate immunity, but diminishes cord blood innate immune functions.

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