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  3. Medizin - Open Access LMU - Teil 20/22 Podcast
  4. The oxidative burst reaction in mammalian cells depends on gravity
Gravity has been a constant force throughout the Earth's
evolutionary history. Thus, one of the fundamental biological
questions is if and how complex cellular and molecular functions of
life on Earth require gravity. In this study, we investigated the
influence of gravity on the oxidative burst reaction in
macrophages, one of the key elements in innate immune response and
cellular signaling. An important step is the production of
superoxide by the NADPH oxidase, which is rapidly converted to H2O2
by spontaneous and enzymatic dismutation. The phagozytosis-mediated
oxidative burst under altered gravity conditions was studied in
NR8383 rat alveolar macrophages by means of a luminol assay.
Ground-based experiments in "functional weightlessness" were
performed using a 2 D clinostat combined with a photomultiplier
(PMT clinostat). The same technical set-up was used during the 13th
DLR and 51st ESA parabolic flight campaign. Furthermore,
hypergravity conditions were provided by using the Multi-Sample
Incubation Centrifuge (MuSIC) and the Short Arm Human Centrifuge
(SAHC). The results demonstrate that release of reactive oxygen
species (ROS) during the oxidative burst reaction depends greatly
on gravity conditions. ROS release is 1.) reduced in microgravity,
2.) enhanced in hypergravity and 3.) responds rapidly and
reversible to altered gravity within seconds. We substantiated the
effect of altered gravity on oxidative burst reaction in two
independent experimental systems, parabolic flights and 2D
clinostat / centrifuge experiments. Furthermore, the results
obtained in simulated microgravity (2D clinorotation experiments)
were proven by experiments in real microgravity as in both cases a
pronounced reduction in ROS was observed. Our experiments indicate
that gravity-sensitive steps are located both in the initial
activation pathways and in the final oxidative burst reaction
itself, which could be explained by the role of cytoskeletal
dynamics in the assembly and function of the NADPH oxidase complex.

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