Department of Medicine, Campus Bio-Medico University of Rome, 00128 Rome, Italy.
European Center for Brain Research, IRCCS Santa Lucia Foundation, 00143 Rome, Italy.
Cells. 2024 Jan 3;13(1):100. doi: 10.3390/cells13010100.
Space-related stressors such as microgravity are associated with cellular and molecular alterations of the immune and inflammatory homeostasis that have been linked to the disorders that astronauts suffer from during their missions. Most of the research of the past 30 years has consistently established that innate adaptive immune cells represent a target of microgravity, which leads to their defective or dysfunctional activation, as well as to an altered ability to produce soluble mediators-e.g., cytokines/chemokines and bioactive lipids-that altogether control tissue homeostasis. Bioactive lipids include a vast array of endogenous molecules of immune origin that control the induction, intensity and outcome of the inflammatory events. However, none of the papers published so far focus on a newly characterized class of lipid mediators called specialized pro-resolving mediators (SPMs), which orchestrate the "resolution of inflammation"-i.e., the active control and confinement of the inflammatory torrent mostly driven by eicosanoids. SPMs are emerging as crucial players in those processes that avoid acute inflammation to degenerate into a chronic event. Given that SPMs, along with their metabolism and signaling, are being increasingly linked to many inflammatory disorders, their study seems of the outmost importance in the research of pathological processes involved in space-related diseases, also with the perspective of developing therapeutic countermeasures. Here, we show that microgravity, simulated in the rotary cell culture system (RCCS) developed by NASA, rearranges SPM receptors both at the gene and protein level, in human monocytes but not in lymphocytes. Moreover, RCCS treatment reduces the biosynthesis of a prominent SPM like resolvin (Rv) D1. These findings strongly suggest that not only microgravity can impair the functioning of immune cells at the level of bioactive lipids directly involved in proper inflammation, but it does so in a cell-specific manner, possibly perturbing immune homeostasis with monocytes being primary targets.
太空相关的应激源，如微重力，与免疫和炎症动态平衡的细胞和分子改变有关，这些改变与宇航员在任务中所患的疾病有关。在过去的 30 年中，大多数研究一致认为先天适应性免疫细胞是微重力的靶点，这导致它们的缺陷或功能失调激活，以及改变产生可溶性介质的能力，例如细胞因子/趋化因子和生物活性脂质，这些共同控制组织动态平衡。生物活性脂质包括控制炎症事件的诱导、强度和结果的大量内源性免疫来源的分子。然而，迄今为止发表的论文都没有关注一类新的脂质介质，称为专门的促解决介质 (SPM)，它协调“炎症解决”-即主要由类二十烷酸驱动的炎症洪流的主动控制和限制。SPM 作为避免急性炎症演变为慢性事件的关键因素出现。鉴于 SPM 及其代谢和信号转导越来越与许多炎症性疾病有关，它们的研究在与太空相关疾病相关的病理过程的研究中似乎至关重要，同时也为开发治疗对策提供了前景。在这里，我们表明，由美国宇航局开发的旋转细胞培养系统 (RCCS) 模拟的微重力在人类单核细胞而非淋巴细胞中重新排列 SPM 受体的基因和蛋白质水平。此外，RCCS 处理会降低一种突出的 SPM 类物质，如 resolvin (Rv) D1 的生物合成。这些发现强烈表明，微重力不仅可以直接影响参与适当炎症的生物活性脂质的免疫细胞的功能，而且是以细胞特异性的方式进行，可能通过单核细胞成为主要靶标来扰乱免疫动态平衡。
