Macrophages in microgravity: the impact of space on immune cells

Abstract

The effects of a microgravity environment on the myriad types of immune cells present within the human body have been assessed both by bench-scale simulation and suborbital methods, as well as in true spaceflight. Macrophages have garnered increased research interest in this context in recent years. Their functionality in both immune response and tissue remodeling makes them a unique cell to investigate in regards to gravisensitive effects as well as parameters of interest that could impact astronaut health. Here, we review and summarize the literature investigating the effects of microgravity on macrophages and monocytes regarding the microgravity environment simulation/generation methods, cell sources, experiment durations, and parameters of interest utilized within the field. We discuss reported findings on the impacts of microgravity on macrophage/monocyte structure, adhesion and migration, proliferation, genetic expression, cytokine secretion, and reactive oxygen species production, as well as polarization. Based on this body of data, we make recommendations to the field for careful consideration of experimental design to complement existing reports, as the multitude of disparate study methods previously published can make drawing direct comparisons difficult. However, the breadth of different testing methodologies can also lend itself to attempting to identify the most robust and consistent responses to microgravity across various testing conditions.

The Effects of Simulated Microgravity on Macrophage Phenotype

“…This agrees with current literature on the downregulation of TNF-α protein expression by macrophages in microgravity [11]. A review of literature highlights the differences in results seen across studies, with some studies reporting increases in TNF-α expression [55][56][57] and others reporting decreases [5,[19][20][21] from µG, suggesting that the variety of cell types, microgravity system, duration, and methods used could be contributing factors [10]. Importantly, when compared to studies using the same cell type and microgravity simulation as our study, TNF-α protein expression is largely reported to decrease.…”

“…Published data on the effect of altered gravity on macrophages have not extensively considered the role of macrophage phenotypes. Macrophage microgravity studies in general have shown variable results and are relatively limited [10,11]. Overall, macrophages demonstrate many sensitivities to changes in gravity, both in their short-and long-term responses.…”

“…Other opportunities to expose cells to real microgravity include suborbital flight/sounding rocket and parabolic flight modalities, however, these face many of the same challenges. Alternatives to real microgravity include a variety of methods commonly used to expose cultured cells to simulated microgravity, including several benchtop methods, such as clinorotation and random position machines [10,11]. In this work, we utilize a rotary cell culture system (RCCS), specifically the rotating wall vessel (RWV) originally developed by the National Aeronautics and Space Administration, to expose phenotypically divergent macrophages to simulated microgravity and assess the acute biological effects.…”

Metabolic Dynamics in Short- and Long-Term Microgravity in Human Primary Macrophages

“…The proteasome system responds rapidly to oxidative stress [93] and could therefore represent an integrative system for different primary and secondary effects of altered gravity. To understand the metabolic homeostasis could therefore shed light on the potential underlying molecular mechanisms of functional deterioration of human macrophages in microgravity, including reduced phagocytic index, reduced engulfing, oxidative bursting and degranulation [94,95], as reviewed in [96]. Integrative omics analysis has the potential to pinpoint certain metabolic mechanisms: intriguingly, Shi et al reported the urea cycle to be among the transcriptional significantly affected pathways in macrophages after 12 days in microgravity, potentially compensating for the increased Ornithine concentrations after five minutes [97].…”

Simulated Microgravity Remodels Extracellular Matrix of Osteocommitted Mesenchymal Stromal Cells

“…Moreover, a loss of bone tissue calcium is aggravated by parathyroid hormone regulation, resulting in reduced calcium reabsorption in the kidneys [7,11]. To study the effects of microgravity on stromal cells, different cell types were applied as well as different approaches to simulate microgravity [12][13][14][15][16].…”