NanoRacks-CellBox-Primary Human Macrophages in Microgravity Environment (NanoRacks-CellBox-PRIME) - 05.30.18

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
Immune cells called macrophages fight illness by attacking and killing bacteria and other foreign invaders in the body. But microgravity, which suppresses the human immune system, can affect how well they work. NanoRacks-CellBox-Primary Human Macrophages in Microgravity Environment (NanoRacks-CellBox-PRIME) studies long-term changes to these cells to better understand how spaceflight affects the immune system.
Science Results for Everyone
Before humans can boldly go where no one has gone before, our macrophages must beat microgravity. Analysis of cellular and molecular changes in these important immune cells shows no significant structural changes in the cell cytoskeleton after longer exposure to microgravity. Results also show reduced expression of the cell-adhesion molecule ICAM-1 and a loss of cell surface-bound fucose (a hexose deoxy sugar involved in cell-to-cell communication). Both factors may contribute to immune cell activation and migration impairments. The lack of long-term cytoskeletal changes, together with stable metabolic function, suggesting cellular adaptation in microgravity, has important implications for human health and performance during long-term missions.

The following content was provided by Oliver Ullrich, Ph.D., M.D, and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: BioRack Experiment Containers

Principal Investigator(s)
Oliver Ullrich, Ph.D., M.D, University of Zurich, Zurich, Switzerland

Co-Investigator(s)/Collaborator(s)
Svantje Tauber, Ph.D., University of Zurich, Zurich, Switzerland
Liliana Layer, M.S., University of Zurich, Zurich, Switzerland
Naomi Shepherd, B.Med., University of Zurich, Zurich, Switzerland
Swantje Hauschild, M.S., University of Zurich, Zurich, Switzerland
Katrin Paulsen, M.D., University of Zurich, Zurich, Switzerland
Cora Thiel, Ph.D., University of Zurich, Zurich, Switzerland

Developer(s)
Astrium Space Transportation, Friedrichshafen, Germany
NanoRacks, LLC, Webster, TX, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Scientific Discovery, Space Exploration, Earth Benefits

ISS Expedition Duration
March 2014 - September 2014

Expeditions Assigned
39/40

Previous Missions
Information Pending

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Experiment Description

Research Overview

  • During space flight, the immune system is one of the most affected systems of the human body.

  • It is necessary to understand the cellular and molecular mechanisms by which microgravity influences and changes the immune cell function during space flight.

  • NanoRacks-CellBox-Primary Human Macrophages in Microgravity Environment (NanoRacks-CellBox-PRIME) investigates microgravity-associated long-term alterations in primary human macrophages, the most important effector cells of the immune system, which are responsible for attacking, and killing bacteria and other foreign and pathogenic intruders in the human body.
     

Description

The immune system is one of the most affected systems of the human body during space flight and cells of the immune system are exceptionally sensitive to microgravity. Thus, serious concerns arise, whether space flight associated weakening of the immune system ultimately precludes the expansion of human presence beyond the Earth's orbit. For human space flight, it is an urgent need to understand the cellular and molecular mechanisms by which altered gravity influences and changes the immune cell function. NanoRacks-CellBox-Primary Human Macrophages in Microgravity Environment (NanoRacks-CellBox-PRIME) investigates the microgravity-associated long-term alterations in primary human macrophages, the most important effector cells of the immune system, which are responsible for attacking, and killing bacteria and other foreign and pathogenic intruders in the human body. Surface molecules are analyzed, which are required for recognition of bacteria and cell-cell communication, and the cytoskeletal architecture is investigated after several days in microgravity. Additionally, secretion products (such as cytokines) and metabolites in the cell culture supernatant are analyzed.
 
Primary human macrophages are attached to polycarbonates-slides on ground and implemented in the hardware, where they are cultured with the respective culture medium. After the incubation phase in space (in microgravity and in 1 g), cells are automatically fixed with 1% paraformaldehyde. After sample return, surface-molecules and components of the cytoskeleton are analyzed and quantified by immunocytochemistry / confocal microscopy. In-flight microgravity and 1g group are compared, in parallel with appropriate ground controls. Parameters to be analyzed are: Actin, vimentin, tubulin, MHCI, MHC-II, CD86, CD36, CD11a, CD11b, CD18 and ICAM-1.  With this experiment, it is possible to assess the influence of microgravity on key molecules of migration, presentation of antigens, cell-cell-communication and activation of the specific immune system. A disturbed cytoskeleton, reduced surface receptors for the activation of T lymphocytes and for antigen presenting molecules could represent a dysfunctional macrophage phenotype, which could be no longer capable of migrating or recognizing and attacking pathogens and to activate the specific immune system.

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Applications

Space Applications
Humans experience several negative physical changes in space, but the immune system takes one of the biggest hits. Future long-duration space missions might be compromised if crew members’ immune systems are severely weakened. Understanding how microgravity changes the immune system at the cellular and molecular level helps scientists design new strategies or treatments to maintain crew health.

Earth Applications
Humans and all other life on Earth evolved in the presence of gravity, which affects how our cells grow and function. This investigation improves knowledge of how human cell structures and behaviors change in the absence of gravity, providing fundamental insight into cell biology.

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Operations

Operational Requirements and Protocols

BioRack Experiment Containers are returned at 4°C.

A crewmember installs BioRack Experiment Containers no later than docking +2 days. After automatic fixation, the containers must remain in the BioRack for a minimum of 12 days prior to the crewmember removing and storing at 4°C for return.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

This study investigated long-term structural and functional changes to human macrophages (i.e., cells that defend the body as part of their immune response) associated with microgravity. More specifically, the study investigated the cytoskeletal architecture, surface molecules for macrophage activation and cell-cell-communication, as well as the metabolite spectrum in the cell culture supernatant (the overlying residual liquid that results after centrifugation). Results showed that cell area and number increased after 11 days in microgravity and there were no quantitative structural changes in the cytoskeleton of macrophages. Additionally, only the expression of one adhesion molecule (ICAM-1) was reduced in microgravity. And finally, of 74 metabolites analyzed in the cell culture, only 8 metabolites revealed significant differences relative to 1g control cells. In particular, the increase of free fucose (a hexose deoxy sugar on the cell surface) in the cell culture supernatant was associated with a decrease of cell surface–bound fucose. The reduced expression of ICAM-1 and the loss of cell surface–bound fucose may contribute to cell activation and migration impairments of the immune response. However, no significant cytoskeletal changes suggest that cellular adaptation is initiated in microgravity. This potential robustness of the cells in microgravity has important implications for human health and performance during long-term missions in space.

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Results Publications

    Tauber S, Lauber BA, Paulsen K, Layer LE, Lehmann M, Hauschild S, Shepherd NR, Polzer J, Segerer J, Thiel CS, Ullrich O.  Cytoskeletal stability and metabolic alterations in primary human macrophages in long-term microgravity. PLOS ONE. 2017 April 18; 12(4): e0175599. DOI: 10.1371/journal.pone.0175599. PMID: 28419128.

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Ground Based Results Publications

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ISS Patents

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Related Publications

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Related Websites
NanoRacks

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Imagery

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Human macrophages, the most important effector cells of the immune system, which are sent to space to evaluate the effect of weightlessness in the current NanoRacks-CellBox-PRIME. The cells are stained for parts of the cytoskeleton (green), cytoplasm (red) and the cell nucleus (blue).  After flight such specific stainings for more than 15 features of the cells shall allow to detect effects that weightlessness causes in these cells. Image courtesy of Oliver Ullrich.

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NASA Image: ISS039E017566 - Expedition 39 Flight Engineer Steve Swanson unpacks NanoRacks BioRack Experiment Containers in preparation for insertion into the BioRack frame in the Kibo Japanese Experiment Pressurized Module (JPM). NanoRacks BioRack contains two investigations. NanoRacks-CellBox-Primary Human Macrophages in Microgravity Environment (NanoRacks-CellBox-PRIME) investigates microgravity-associated long-term alterations in primary human macrophages, which are responsible for attacking, and killing bacteria and other foreign and pathogenic intruders in the human body. NanoRacks-CellBox-Effect of Microgravity on Human Thyroid Carcinoma Cells (NanoRacks-CellBox-Thyroid Cancer) investigates the effects of microgravity on human thyroid carcinoma cells.

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