Lymphocytes on sounding rockets

Cogoli, Marianne; Bechler, B.; Cogoli, Augusto; Arena, N; Barni, Sergio; Pippia, P; Sechi, Gian Pietro; Valora, N.; Monti, R.

doi:10.1016/0273-1177(92)90276-4

Cited by 18 publications

(5 citation statements)

References 2 publications

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“…In lymphocytes, microgravity affected the protein kinase C [10,11], but not the patching and capping of conA-binding membrane proteins [12], influenced NF-kB and MAPK-signaling [13] and the expression of the early oncogenes c-fos, c-myc and c-jun (summarized in [14]). Other studies demonstrated pro- and antiapoptotic effects of altered gravity in human mononuclear cells [15], human ML-1 thyroid-carcinoma cells [16], and astrocytes [17] and influences on fas, p53, bax and bcl-2 were described [16,18,20].…”

Section: Discussionmentioning

confidence: 99%

Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity

et al. 2012

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In our study we aimed to identify rapidly reacting gravity-responsive mechanisms in mammalian cells in order to understand if and how altered gravity is translated into a cellular response. In a combination of experiments using "functional weightlessness" provided by 2D-clinostats and real microgravity provided by several parabolic flight campaigns and compared to in-flight-1g-controls, we identified rapid gravity-responsive reactions inside the cell cycle regulatory machinery of human T lymphocytes. In response to 2D clinorotation, we detected an enhanced expression of p21 Waf1/Cip1 protein within minutes, less cdc25C protein expression and enhanced Ser147-phosphorylation of cyclinB1 after CD3/CD28 stimulation. Additionally, during 2D clinorotation, Tyr-15-phosphorylation occurred later and was shorter than in the 1 g controls. In CD3/CD28-stimulated primary human T cells, mRNA expression of the cell cycle arrest protein p21 increased 4.1-fold after 20s real microgravity in primary CD4+ T cells and 2.9-fold in Jurkat T cells, compared to 1 g in-flight controls after CD3/CD28 stimulation. The histone acetyltransferase (HAT) inhibitor curcumin was able to abrogate microgravity-induced p21 mRNA expression, whereas expression was enhanced by a histone deacetylase (HDAC) inhibitor. Therefore, we suppose that cell cycle progression in human T lymphocytes requires Earth gravity and that the disturbed expression of cell cycle regulatory proteins could contribute to the breakdown of the human immune system in space.

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Section: Discussionmentioning

confidence: 99%

Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity

et al. 2012

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“…The first possible explanation for the depression of T cell activation is that the binding of the mitogen is altered under low G conditions. To study the binding of Con A and the formation of patches and caps of Con A receptors, Cogoli's groups [98,99] performed experiments on sounding rockets. Fluorescent-labeled Con A was added to cells as soon as lowgravity conditions were established or a few minutes after the onset of microgravity.…”

Section: T Cells In Low-gravity Conditionsmentioning

confidence: 99%

“…Fluorescent-labeled Con A was added to cells as soon as lowgravity conditions were established or a few minutes after the onset of microgravity. Two experiments were performed, one with lymphocytes purified from human peripheral blood [98] and one with the Jurkat T cell line [99]. All demonstrated that the influence of low gravity on the delivery of the first signal of activation is rather small and that rapid processes such as mitogen binding, patching, and probably capping are not involved in the depression of the in vitro activation of T lymphocytes [100].…”

Section: T Cells In Low-gravity Conditionsmentioning

confidence: 99%

Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond Earth’s orbit?

Guéguinou

Huin-Schohn

Bascove³

et al. 2009

Journal of Leukocyte Biology

255

177

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This year, we celebrate the 40th birthday of the first landing of humans on the moon. By 2020, astronauts should return to the lunar surface and establish an outpost there that will provide a technical basis for future manned missions to Mars. This paper summarizes major constraints associated with a trip to Mars, presents immunological hazards associated with this type of mission, and shows that our current understanding of the immunosuppressive effects of spaceflight is limited. Weakening of the immune system associated with spaceflight is therefore an area that should be considered more thoroughly before we undertake prolonged space voyages.

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“…Experiments on board Spacelab 1 demonstrated that human PBLs stimulated with the T cell mitogen Con A for 3 days in spaceflight had profoundly suppressed T cell proliferation compared with ground controls, as measured by 3 H-thymidine incorporation [18]. Sounding rocket experiments showed that fluorescently tagged Con A bound to T cells normally in g, and the processes of patching and capping were comparable between 1g and g conditions [19], indicating that inhibition of T cell proliferation was not at the level of agonist binding. Follow-up spaceflight experiments demonstrated that PBLs stimulated with Con A in g produced significantly lower levels of IL-2, IL-2R, IFN-␥, and TNF [20] and that exogenous addition of IL-2 did not rescue proliferative activity in g [21].…”

Section: Introductionmentioning

confidence: 99%

The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity

Chang

Walther

et al. 2012

Journal of Leukocyte Biology

111

120

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This study tested the hypothesis that transcription of immediate early genes is inhibited in T cells activated in μg. Immunosuppression during spaceflight is a major barrier to safe, long-term human space habitation and travel. The goals of these experiments were to prove that μg was the cause of impaired T cell activation during spaceflight, as well as understand the mechanisms controlling early T cell activation. T cells from four human donors were stimulated with Con A and anti-CD28 on board the ISS. An on-board centrifuge was used to generate a 1g simultaneous control to isolate the effects of μg from other variables of spaceflight. Microarray expression analysis after 1.5 h of activation demonstrated that μg- and 1g-activated T cells had distinct patterns of global gene expression and identified 47 genes that were significantly, differentially down-regulated in μg. Importantly, several key immediate early genes were inhibited in μg. In particular, transactivation of Rel/NF-κB, CREB, and SRF gene targets were down-regulated. Expression of cREL gene targets were significantly inhibited, and transcription of cREL itself was reduced significantly in μg and upon anti-CD3/anti-CD28 stimulation in simulated μg. Analysis of gene connectivity indicated that the TNF pathway is a major early downstream effector pathway inhibited in μg and may lead to ineffective proinflammatory host defenses against infectious pathogens during spaceflight. Results from these experiments indicate that μg was the causative factor for impaired T cell activation during spaceflight by inhibiting transactivation of key immediate early genes.

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Lymphocytes on sounding rockets

Cited by 18 publications

References 2 publications

Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity

Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity

Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond Earth’s orbit?

The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity

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