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Published on: May 31, 2018
Microgravity activates monocyte ERK1/2 signaling and modulates the response to lipopolysaccharide
Ruslan A Mammadov1,2, Melle P C van Hulten1, Max K Bakker1
1Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Background:
Microgravity alters immune cell function, potentially compromising host defense during spaceflight. Because appropriate immune regulation is also critical in chronic inflammatory and autoimmune conditions, insights from spaceflight biology may have broader implications for human health. Monocyte activation via the p44/42 MAPK pathway is central to inflammatory responses, yet the influence of microgravity on this signaling cascade remains incompletely understood. This study aimed to determine how microgravity affects basal and lipopolysaccharide (LPS)-stimulated ERK1/2 kinases (also known as p44/42 MAP kinases) activity in human monocytes, focusing on signaling state redistribution at both single-cell and population levels.
Methods:
Monocytes were cultured during spaceflight under either normal gravity (1G) or microgravity (µG) and exposed to LPS or control conditions. MAPK activity was quantified and analysed to assess basal signaling, stimulus responsiveness, and variability within the population.
Results:
Basal MAPK activity was significantly elevated in µG compared with 1G monocytes (p = 0.0181). LPS stimulation robustly increased MAPK activity in 1G cells (p = 0.0267) but not in µG (p = 0.6752). Although baseline signaling was higher in µG, LPS responses in µG and 1G were not significantly different (p = 0.7905). Under microgravity, the cell population displayed broader signaling distribution and a larger non-responsive fraction. Although baseline signaling was higher in µG net LPS responsiveness was diminished compared with 1G.
Conclusion:
Microgravity redistributes monocyte signaling states, increasing basal ERK1/2 activity while attenuating rapid stimulus-induced activation and expanding the non-responsive cell fraction. These findings provide new mechanistic insight into how microgravity shapes immune signaling and highlight cellular heterogenety as a critical determinant of immune regulation during spaceflight.
Insights
Microgravity increases basal ERK1/2 activity in monocytes but impairs their response to LPS stimulation. This spaceflight-induced immune dysregulation highlights cellular heterogeneity in immune responses.
Area of Science:
- Space biology
- Immunology
- Cellular signaling
Background:
- Spaceflight-induced microgravity alters immune cell function, potentially impairing host defense.
- Monocyte activation via the p44/42 MAPK pathway is crucial for inflammatory responses.
- Understanding microgravity's effect on this pathway offers insights into immune regulation and inflammatory conditions.
Purpose of the Study:
- To investigate the impact of microgravity on basal and lipopolysaccharide (LPS)-stimulated ERK1/2 (p44/42 MAPK) activity in human monocytes.
- To analyze how microgravity affects single-cell and population-level signaling states.
Main Methods:
- Human monocytes were cultured under normal gravity (1G) and microgravity (µG) conditions during spaceflight.
- Cells were stimulated with LPS or control conditions.
- MAPK activity was quantified to assess basal signaling, stimulus responsiveness, and population variability.
Main Results:
- Basal MAPK activity was significantly elevated in microgravity (µG) compared to 1G.
- LPS stimulation increased MAPK activity in 1G but not in µG monocytes.
- Microgravity led to broader signaling distribution and a larger non-responsive monocyte fraction, diminishing net LPS responsiveness.
Conclusions:
- Microgravity alters monocyte signaling states, increasing basal ERK1/2 activity.
- Stimulus-induced activation is attenuated, and the non-responsive cell fraction expands under microgravity.
- Cellular heterogeneity is a key factor in immune regulation during spaceflight.
