title: Signal transduction in primary human T lymphocytes in altered gravity - results of the MASER-12 suborbital space flight mission.
abstract: We investigated the influence of altered gravity on key proteins of T cell activation during the MASER-12 ballistic suborbital rocket mission of the European Space Agency (ESA) and the Swedish Space Cooperation (SSC) at ESRANGE Space Center (Kiruna, Sweden). We quantified components of the T cell receptor, the membrane proximal signaling, MAPK-signaling, IL-2R, histone modifications and the cytoskeleton in non-activated and in ConA/CD28-activated primary human T lymphocytes. The hypergravity phase during the launch resulted in a downregulation of the IL-2 and CD3 receptor and reduction of tyrosine phosphorylation, p44/42-MAPK phosphorylation and histone H3 acetylation, whereas LAT phosphorylation was increased. Compared to the baseline situation at the point of entry into the microgravity phase, CD3 and IL-2 receptor expression at the surface of non-activated T cells were reduced after 6 min microgravity. Importantly, p44/42-MAPK-phosphorylation was also reduced after 6 min microgravity compared to the 1g ground controls, but also in direct comparison between the in-flight μg and the 1g group. In activated T cells, the reduced CD3 and IL-2 receptor expression at the baseline situation recovered significantly during in-flight 1g conditions, but not during microgravity conditions. Beta-tubulin increased significantly after onset of microgravity until the end of the microgravity phase, but not in the in-flight 1g condition. This study suggests that key proteins of T cell signal modules are not severely disturbed in microgravity. Instead, it can be supposed that the strong T cell inhibiting signal occurs downstream from membrane proximal signaling, such as at the transcriptional level as described recently. However, the MASER-12 experiment could identify signal molecules, which are sensitive to altered gravity, and indicates that gravity is obviously not only a requirement for transcriptional processes as described before, but also for specific phosphorylation / dephosphorylation of signal molecules and surface receptor dynamics.
authors: Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, Zurich, CH-8057, Switzerland. oliver.ullrich@uzh.ch.
authors: Svantje
authors: S
authors: Tauber
authors: Swantje
authors: S
authors: Hauschild
authors: Claudia
authors: C
authors: Crescio
authors: Christian
authors: C
authors: Secchi
authors: Katrin
authors: K
authors: Paulsen
authors: Antonella
authors: A
authors: Pantaleo
authors: Angela
authors: A
authors: Saba
authors: Isabell
authors: I
authors: Buttron
authors: Cora Sandra
authors: CS
authors: Thiel
authors: Augusto
authors: A
authors: Cogoli
authors: Proto
authors: P
authors: Pippia
authors: Oliver
authors: O
authors: Ullrich
references: Science. 1984 Jul 13;225(4658):228-30
references: 6729481
references: Adv Space Res. 1999;24(6):801-5
references: 11542625
references: FASEB J. 1999 Nov;13(14):2071-82
references: 10544190
references: Astrobiology. 2013 Jan;13(1):1-17
references: 23252378
references: Acta Astronaut. 2001 Aug-Nov;49(3-10):399-418
references: 11669127
references: Adv Space Biol Med. 1997;6:33-79
references: 9048133
references: Adv Immunol. 1998;70:1-81
references: 9755337
references: J Cell Biochem. 2010 Sep 1;111(1):123-9
references: 20506542
references: Kosm Biol Med. 1973 Nov-Dec;7(6):35-40
references: 4779034
references: FASEB J. 2005 Dec;19(14):2020-2
references: 16210397
references: J Gravit Physiol. 2002 Jul;9(1):P275-6
references: 15002578
references: Aviat Space Environ Med. 2008 Sep;79(9):835-43
references: 18785351
references: Adv Space Res. 2003;32(8):1585-93
references: 15002415
references: J Immunol. 1994 Jul 1;153(1):63-72
references: 8207256
references: Cell Commun Signal. 2012 Jan 24;10(1):1
references: 22273506
references: Adv Space Res. 1999;24(6):793-800
references: 11542624
references: Protoplasma. 2006 Dec;229(2-4):243-9
references: 17180508
references: J Exp Med. 1987 Apr 1;165(4):1141-59
references: 3104527
references: Biotechnol Bioeng. 1992 Oct 20;40(8):991-6
references: 11538710
references: Cell Immunol. 1988 Nov;117(1):12-21
references: 2972393
references: Hum Exp Toxicol. 1996 Jun;15(6):504-7
references: 8793534
references: Sleep. 2005 Oct;28(10):1312-6
references: 16295217
references: J Leukoc Biol. 1993 May;53(5):569-75
references: 8501396
references: FEBS Lett. 1998 Sep 25;436(1):115-8
references: 9771904
references: J Med Virol. 2008 Jun;80(6):1116-22
references: 18428120
references: J Gravit Physiol. 1996 Apr;3(1):1-9
references: 11539302
references: J Med Virol. 2004 Jan;72(1):174-9
references: 14635028
references: FASEB J. 1996 Dec;10(14):1627-34
references: 9002555
references: Ann N Y Acad Sci. 2009 Apr;1161:135-46
references: 19426312
references: Aviakosm Ekolog Med. 2011 Jul-Aug;45(4):39-41
references: 21970042
references: J Leukoc Biol. 2001 May;69(5):755-61
references: 11358984
references: Proc Natl Acad Sci U S A. 1985 Dec;82(23):8158-62
references: 3934668
references: Biochim Biophys Acta. 2003 Oct 21;1642(3):173-9
references: 14572900
references: PLoS One. 2009 Dec 16;4(12):e8332
references: 20016778
references: Bol Asoc Med P R. 2006 Jul-Sep;98(3):223-8
references: 19610562
references: Eur Biophys J. 2006 May;35(5):393-400
references: 16496137
references: J Leukoc Biol. 2009 Nov;86(5):1027-38
references: 19690292
references: J Leukoc Biol. 2012 Dec;92(6):1133-45
references: 22750545
references: J Biotechnol. 1996 Jun 27;47(2-3):215-22
references: 8987568
references: Protoplasma. 2006 Dec;229(2-4):225-34
references: 17180506
references: J Cell Biochem. 2010 Apr 15;109(6):1201-9
references: 20127722
references: In Vitro Cell Dev Biol Anim. 2009 Dec;45(10):622-32
references: 19609626
references: J Biol Chem. 2011 Sep 16;286(37):32483-90
references: 21775437
references: Adv Space Res. 1999;23(12):1945-53
references: 11710376