Signal transduction in T lymphocytes — A comparison of the data from space, the free fall machine and the random positioning machine

Schwarzenberg, M.; Pippia, P; Meloni, Maria Antonia; Cossu, Gianfranco; Cogoli-Greuter, Marianne; Cogoli, Augusto

doi:10.1016/s0273-1177(99)00075-7

Cited by 93 publications

(64 citation statements)

References 9 publications

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“…Shear force is generated in all the rotating devices. However, the experiments here described have been carried out utilizing culture chambers that almost completely exclude the presence of air bubbles by means of a mobile piston, thus shear effects are significantly reduced and do not affect appreciably the results [Schwarzenberg et al, 1999]. In conclusion, there is convincing experimental evidence on the validity of the model here used to produce modeled microgravity conditions.…”

Section: Discussionmentioning

confidence: 70%

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Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells

et al. 2006

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Gravity acts permanently on organisms as either static or dynamic stimulation. Understanding the influence of gravitational and mechanical stimuli on biological systems is an intriguing scientific problem. More than two decades of life science studies in low g, either real or modeled by clinostats, as well as experimentation with devices simulating different types of controlled mechanical stimuli, have shown that important biological functions are altered at the single cell level. Here, we show that the human leukemic line FLG 29.1, characterized as an osteoclastic precursor model, is directly sensitive to gravitational unloading, modeled by a random positioning machine (RPM). The phenotypic expression of cytoskeletal proteins, osteoclastic markers, and factors regulating apoptosis was investigated using histochemical and immunohistochemical methods, while the expression of the corresponding genes was analyzed using RT-PCR. A quantitative bone resorption assay was performed. Autofluorescence spectroscopy and imaging were applied to gain information on cell metabolism. The results show that modeled hypogravity may trigger both differentiation and apoptosis in FLG 29.1 cells. Indeed, when comparing RPM versus 1 Â g cultures, in the former we found cytoskeletal alterations and a marked increase in apoptosis, but the surviving cells showed an osteoclastic-like morphology, overexpression of osteoclastic markers and the ability to resorb bone. In particular, the overexpression of both RANK and its ligand RANKL, maintained even after return to 1 Â g conditions, is consistent with the firing of a differentiation process via a paracrine/autocrine mechanism. J. Cell. Biochem. 98: 65-80, 2006. ß 2005 Wiley-Liss, Inc.Key words: weightlessness; preosteoclastic differentiation; apoptosis; bone resorption; osteoporosis; gene expressionThe importance of gravity in modulating some biological processes, such as plant gravitropism and the adaptation of the vertebrate skeleton in relation to its load-bearing function, has long been known. Nevertheless, the role of gravity and other mechanical factors in biological processes is far from clear. A weightless environment is a powerful tool for understanding this role and for studying the related cellular and molecular mechanisms. Several investigations conducted in space laboratories and with instruments averaging the gravity vector, and thus simulating conditions of reduced gravity, have shown that isolated cells may change their behavior under altered gravitational conditions. Loss of cell activation [Cogoli et al., 1984], perturbation of signal transduction [Schmitt et al., 1996;Hashemi et al., 1999] and modification of genetic expression [Walther et al., 1998;Hammond et al., 1999] have been described. This suggests that some of the mechanisms at the roots of the systemic effects observed in weightlessness, such as depression of the immune system [Gmü nder and Cogoli, 1996]

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Section: Discussionmentioning

confidence: 70%

“…during exposure of cells to microgravity has been proved by comparing data obtained in space experiments with those obtained in the RPM, as well as in other rotating devices [Cooper and Pellis, 1998;Schwarzenberg et al, 1999].…”

Section: Discussionmentioning

confidence: 99%

Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells

et al. 2006

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“…The random rotation in all directions results in a net force of zero. Simulation of weightlessness with the RPM was reported to result in a wide variety of cellular responses which have also been found partly under real microgravity conditions (Hoson et al 1997;Schwarzenberg et al 1998;Grimm et al 2002;Uva et al 2002;Infanger et al 2006;Ulbrich et al 2008;Versari et al 2007a, b).…”

Section: Introductionmentioning

confidence: 93%

Simulation of Microgravity by Magnetic Levitation and Random Positioning: Effect on Human A431 Cell Morphology

Moes

Gielen

Bleichrodt

et al. 2010

Microgravity Sci. Technol.

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Simulation of weightlessness is a desired replenishment for research in microgravity since access to space flights is limited. In real microgravity conditions, the human epidermoid cell line A431 exhibits specific changes in the actin cytoskeleton resulting ultimately in the rounding-up of cells. This rounding of A431 cells was studied in detail during exposure to Random Positioning Machine (RPM) rotation and magnetic levitation. Random rotation and magnetic levitation induced similar changes in the actin morphology of A431 cells that were also described in real microgravity. A transient process of cell rounding and renewed spreading was observed in time, illustrated by a changing actin cytoskeleton and variation in the presence of focal adhesions. However, side effects of both methods easily can lead to false linking of cellular responses to simulated microgravity. Therefore further characterization of both methods is required.

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“…Consequently, the impairment of lymphocyte activation and the resulting immune deficiency is considered as a serious limitation for manned long-term space flights [8]. Many studies have revealed strong effects of microgravity on immune cell function [9,10,11], which were performed during manned space flights, on board of orbital, suborbital (sounding rockets) and parabolic flights, and were supported by ground-based facilities for simulation of microgravity such as clinorotation and 3D-random positioning machines [12]. Gravity-sensitivity in T lymphocytes was found for the cell cycle regulation [13], epigenetic regulation [14], chromatin regulation [15], expression profile of microRNA [16], cell motility [17], regulation of apoptosis [18], expression of cytokines [19], and expression of early genes of T lymphocyte activation, which are regulated primarily by the transcription factors NF-κB, CREB, ELK, AP-1, and STAT [13,20,21].…”

Section: Introductionmentioning

confidence: 99%

Signal Transduction in Primary Human T Lymphocytes in Altered Gravity During Parabolic Flight and Clinostat Experiments

Tauber

Hauschild

Paulsen

et al. 2015

Cell Physiol Biochem

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Background/Aims: Several limiting factors for human health and performance in microgravity have been clearly identified arising from the immune system, and substantial research activities are required in order to provide the basic information for appropriate integrated risk management. The gravity-sensitive nature of cells of the immune system renders them an ideal biological model in search for general gravity-sensitive mechanisms and to understand how the architecture and function of human cells is related to the gravitational force and therefore adapted to life on Earth. Methods: We investigated the influence of altered gravity in parabolic flight and 2D clinostat experiments on key proteins of activation and signaling in primary T lymphocytes. We quantified components of the signaling cascade 1.) in non-activated T lymphocytes to assess the “basal status” of the cascade and 2.) in the process of activation to assess the signal transduction. Results: We found a rapid decrease of CD3 and IL-2R surface expression and reduced p-LAT after 20 seconds of altered gravity in non-activated primary T lymphocytes during parabolic flight. Furthermore, we observed decreased CD3 surface expression, reduced ZAP-70 abundance and increased histone H3-acetylation in activated T lymphocytes after 5 minutes of clinorotation and a transient downregulation of CD3 and stable downregulation of IL-2R during 60 minutes of clinorotation. Conclusion: CD3 and IL-2R are downregulated in primary T lymphocytes in altered gravity. We assume that a gravity condition around 1g is required for the expression of key surface receptors and appropriate regulation of signal molecules in T lymphocytes.

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Signal transduction in T lymphocytes — A comparison of the data from space, the free fall machine and the random positioning machine

Cited by 93 publications

References 9 publications

Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells

Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells

Simulation of Microgravity by Magnetic Levitation and Random Positioning: Effect on Human A431 Cell Morphology

Signal Transduction in Primary Human T Lymphocytes in Altered Gravity During Parabolic Flight and Clinostat Experiments

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