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An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization

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Simulated Microgravity Affects Pro-Resolving Properties of Primary Human Monocytes.

Alessandro Leuti^1,2, Marina Fava^2,3, Niccolò Pellegrini¹

¹Department of Medicine, Campus Bio-Medico University of Rome, 00128 Rome, Italy.

|January 11, 2024

Summary

Microgravity impairs immune cell function by altering specialized pro-resolving mediators (SPMs) and their receptors, particularly in monocytes. This suggests a cell-specific mechanism contributing to immune dysregulation in space.

Keywords:

microgravity monocytes resolution of inflammation resolvins specialized pro-resolving mediators

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Area of Science:

Space biology and immunology
Inflammation and resolution biology
Cellular and molecular medicine

Background:

Space-related stressors, like microgravity, disrupt immune and inflammatory homeostasis, contributing to astronaut health issues.
Microgravity affects immune cell activation and the production of soluble mediators, including bioactive lipids that regulate tissue homeostasis.
Specialized pro-resolving mediators (SPMs) are critical for resolving inflammation, preventing chronic inflammatory conditions.

Purpose of the Study:

To investigate the impact of microgravity on SPM receptors and biosynthesis in human immune cells.
To determine if microgravity affects immune cells in a cell-specific manner regarding SPM pathways.
To explore potential mechanisms underlying immune dysregulation in spaceflight and identify therapeutic targets.

Main Methods:

Simulated microgravity using NASA's Rotary Cell Culture System (RCCS) on human monocytes and lymphocytes.
Analysis of SPM receptor expression at both gene and protein levels.
Quantification of SPM biosynthesis, focusing on resolvin (Rv) D1.

Main Results:

Microgravity simulation rearranged SPM receptors at the gene and protein levels in human monocytes, but not lymphocytes.
RCCS treatment significantly reduced the biosynthesis of resolvin (Rv) D1 in the studied cells.
These alterations suggest a cell-specific impact of microgravity on lipid mediators crucial for inflammation resolution.

Conclusions:

Microgravity impairs immune cell function by affecting bioactive lipids and their receptors, with monocytes being primary targets.
The cell-specific perturbation of SPM pathways by microgravity may contribute to immune homeostasis disruption during space missions.
Understanding these mechanisms is crucial for developing countermeasures against space-related immune disorders.