The Effects of Simulated Microgravity on Macrophage Phenotype.

Christopher Ludtka,Erika Moore,Josephine B Allen

doi:10.3390/biomedicines9091205

Abstract

The effects of spaceflight, including prolonged exposure to microgravity, can have significant effects on the immune system and human health. Altered immune cell function can lead to adverse health events, though precisely how and to what extent a microgravity environment impacts these cells remains uncertain. Macrophages, a key immune cell, effect the inflammatory response as well as tissue remodeling and repair. Specifically, macrophage function can be dictated by phenotype that can exist between spectrums of M0 macrophage: the classically activated, pro-inflammatory M1, and the alternatively activated, pro-healing M2 phenotypes. This work assesses the effects of simulated microgravity via clinorotation on M0, M1, and M2 macrophage phenotypes. We focus on phenotypic, inflammatory, and angiogenic gene and protein expression. Our results show that across all three phenotypes, microgravity results in a decrease in TNF-α expression and an increase in IL-12 and VEGF expression. IL-10 was also significantly increased in M1 and M2, but not M0 macrophages. The phenotypic cytokine expression profiles observed may be related to specific gravisensitive signal transduction pathways previously implicated in microgravity regulation of macrophage gene and protein expression. Our results highlight the far-reaching effects that simulated microgravity has on macrophage function and provides insight into macrophage phenotypic function in microgravity.

Highlights

Understanding the effects of the space environment on cellular behavior is critical when considering human health in the context of spaceflight [1,2]
The levels of secreted IL-10 and IL-12 by M2 macrophages cultured in simulated μG was increased over the level secreted by cells cultured in normal (1G) control. As it relates to the angiogenic function, the data show that the M2 phenotype macrophages culture in simulated μG do not have an increase in the amount of vascular endothelial growth factor (VEGF) secreted relative to normal 1G control. (Figure 5B) These results demonstrate similar trends in cytokine production and secretion under conditions of microgravity, we once again see the stimulated secretion of both a pro-inflammatory cytokine (IL-12) and an anti-inflammatory cytokine (IL-10), which again suggests the presence of multiple phenotypes during simulated microgravity culture
Microgravity is a simulated environment that has demonstrable effects on immunology at both the physiological and cellular level. Understanding the effects this environment has on major immune cell types, such as macrophages, informs our understanding of human health in microgravity as well as cell functionality and behavior

Summary

Introduction

Understanding the effects of the space environment on cellular behavior is critical when considering human health in the context of spaceflight [1,2]. The effects of altered gravity on human, animal, and plant cells are frequently reported to have demonstrable effects on cellular function and expression profiles [3,4]. Among the cell types being evaluated, immune cells are of particular interest due to their critical role in pathology and human health [5,6]. Macrophage immune cells are present in the majority of tissues throughout the body and are involved in immunological functions as well as tissue remodeling. Phenotypic differences in macrophages inform their function

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Conclusion