TY  - JOUR
A1  - Twisselmann, Nele
A1  - Pagel, Julia
A1  - Künstner, Axel
A1  - Weckmann, Markus
A1  - Hartz, Annika
A1  - Glaser, Kirsten
A1  - Hilgendorff, Anne
A1  - Göpel, Wolfgang
A1  - Busch, Hauke
A1  - Herting, Egbert
A1  - Weinberg, Jason B.
A1  - Härtel, Christoph
T1  - Hyperoxia/Hypoxia Exposure Primes a Sustained Pro-Inflammatory Profile of Preterm Infant Macrophages Upon LPS Stimulation
JF  - Frontiers in Immunology
N2  - Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O\(_2\)) and infections. We hypothesized that dysregulated macrophage (MФ) activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants. Therefore, we aimed to determine age-dependent differences in immune responses of monocyte-derived MФ comparing cord blood samples derived from preterm (n=14) and term (n=19) infants as well as peripheral blood samples from healthy adults (n=17) after lipopolysaccharide (LPS) exposure. Compared to term and adult MФ, LPS-stimulated preterm MФ showed an enhanced and sustained pro-inflammatory immune response determined by transcriptome analysis, cytokine release inducing a RORC upregulation due to T cell polarization of neonatal T cells, and TLR4 surface expression. In addition, a double-hit model was developed to study pulmonary relevant exposure factors by priming MФ with hyperoxia (O\(_2\) = 65%) or hypoxia (O\(_2\) = 3%) followed by lipopolysaccharide (LPS, 100ng/ml). When primed by 65% O\(_2\), subsequent LPS stimulation in preterm MФ led to an exaggerated pro-inflammatory response (e.g. increased HLA-DR expression and cytokine release) compared to LPS stimulation alone. Both, exposure to 65% or 3% O\(_2\) together with subsequent LPS stimulation, resulted in an exaggerated pro-inflammatory response of preterm MФ determined by transcriptome analysis. Downregulation of two major transcriptional factors, early growth response gene (Egr)-2 and growth factor independence 1 (Gfi1), were identified to play a role in the exaggerated pro-inflammatory response of preterm MФ to LPS insult after priming with 65% or 3% O\(_2\). Preterm MФ responses to LPS and hyperoxia/hypoxia suggest their involvement in excessive inflammation due to age-dependent differences, potentially mediated by downregulation of Egr2 and Gfi1 in the developing lung.
KW  - preterm infants
KW  - sustained inflammation
KW  - macrophages
KW  - hyperoxia
KW  - hypoxia
KW  - infection
KW  - bronchopulmonary dysplasia
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250356
SN  - 1664-3224
VL  - 12
ER  - 
TY  - JOUR
A1  - Zinner, Christoph
A1  - Hauser, Anna
A1  - Born, Dennis-Peter
A1  - Wehrlin, Jon P.
A1  - Holmberg, Hans-Christer
A1  - Sperlich, Billy
T1  - Influence of Hypoxic Interval Training and Hyperoxic Recovery on Muscle Activation and Oxygenation in Connection with Double-Poling Exercise
JF  - PLoS One
N2  - Here, we evaluated the influence of breathing oxygen at different partial pressures during recovery from exercise on performance at sea-level and a simulated altitude of 1800 m, as reflected in activation of different upper body muscles, and oxygenation of the m. triceps brachii. Ten well-trained, male endurance athletes (25.3±4.1 yrs; 179.2±4.5 cm; 74.2±3.4 kg) performed four test trials, each involving three 3-min sessions on a double-poling ergometer with 3-min intervals of recovery. One trial was conducted entirely under normoxic (No) and another under hypoxic conditions \((Ho; F_iO_2 = 0.165)\). In the third and fourth trials, the exercise was performed in normoxia and hypoxia, respectively, with hyperoxic recovery \((HOX; F_iO_2 = 1.00)\) in both cases. Arterial hemoglobin saturation was higher under the two HOX conditions than without HOX (p<0.05). Integrated muscle electrical activity was not influenced by the oxygen content (best d = 0.51). Furthermore, the only difference in tissue saturation index measured via near-infrared spectroscopy observed was between the recovery periods during the NoNo and HoHOX interventions (P<0.05, d = 0.93). In the case of HoHo the athletes’ \(P_{mean}\) declined from the first to the third interval (P < 0.05), whereas Pmean was unaltered under the HoHOX, NoHOX and NoNo conditions. We conclude that the less pronounced decline in \(P_{mean}\) during 3 x 3-min double-poling sprints in normoxia and hypoxia with hyperoxic recovery is not related to changes in muscle activity or oxygenation. Moreover, we conclude that hyperoxia \((F_iO_2 = 1.00)\) used in conjunction with hypoxic or normoxic work intervals may serve as an effective aid when inhaled during the subsequent recovery intervals.
KW  - triceps
KW  - bood
KW  - medical hypoxia
KW  - blood
KW  - arms
KW  - hyperoxia
KW  - breathing
KW  - near-infrared spectroscopy
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126299
VL  - 10
IS  - 10
ER  -