Use of In Vitro Cell Culture Models to Understand the Cellular and Molecular Basis of Immune Dysfunction During Spaceflight

Tauber, Svantje; Yi, Buqing; Choukèr, Alexander; Ullrich, Oliver

doi:10.1007/978-1-4939-3277-1_6

Cited by 1 publication

(6 citation statements)

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“…A generally recognized concept explaining the effect of microgravity on ICAM‐1 expression is not yet available. Papers exploring in vitro models have reported enhanced ICAM‐1 expression on ECs exposed to microgravity . Our results provide some support for these observations.…”

Section: Discussionsupporting

confidence: 86%

“…Papers exploring in vitro models have reported enhanced ICAM-1 expression on ECs exposed to microgravity. 12,42 Our results provide some support for these observations. After a 24 h exposure to the RPM, we detected enhanced expression of the ICAM-1 gene and increased levels of its protein on the surface of non-activated ECs.…”

Section: Discussionsupporting

confidence: 72%

“…Investigations of the endothelium of blood vessels, which is involved in maintaining vessel integrity and function, are important to obtain a better understanding of cardiovascular changes that may occur in space. From this perspective, cultured endothelial cells are viewed as an adequate model for studying molecular mechanisms of gravireception …”

Section: Discussionmentioning

confidence: 99%

“…From this perspective, cultured endothelial cells are viewed as an adequate model for studying molecular mechanisms of gravireception. 8,12,18,23 The purpose of the present study was to evaluate the effects of SMG on the adhesion molecules responsible for both homotypic and heterotypic contacts between intact and TNF-α-activated ECs. EC-EC interactions are responsible for angiogenic and barrier functions, whereas EC contacts with blood cells are involved in immune reactions.…”

Section: Discussionmentioning

confidence: 99%

“…2D-and 3D-clinorotation (generated by Random Positioning Machine (RPM) are the best methods for simulating the effects of microgravity (SMG). 11,12 RPM experiments performed by several groups, including our laboratory, discovered early and delayed changes in ECs. 8,[13][14][15][16][17][18][19] Under RPM conditions, EC growth is accompanied by the formation of unique threedimensional structures that resemble tubules and tissue-like aggregates on the endothelium surface.…”

Section: Introductionmentioning

confidence: 99%

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The ICAM‐1 expression level determines the susceptibility of human endothelial cells to simulated microgravity

Буравкова

Rudimov

Andreeva

et al. 2017

J of Cellular Biochemistry

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Microgravity is a principal risk factor hampering human cardiovascular regulation during space flights. Endothelial dysfunction associated with the impaired integrity and uniformity of the monolayer represents a potential trigger for vascular damage. We characterized the expression profile of the multi-step cascade of adhesion molecules (ICAM-1, VCAM-1, E-selectin, VE-cadherin) in umbilical cord endothelial cells (ECs) after 24 h of exposure to simulated microgravity (SMG), pro-inflammatory cytokine TNF-α, and the combination of the two. Random Positioning Machine (RPM)-mediated SMG was used to mimic microgravity effects. SMG stimulated the expression of E-selectin, which is known to be involved in slowing leukocyte rolling. Primary ECs displayed heterogeneity with respect to the proportion of ICAM-1-positive cells. ECs were divided into two groups: pre-activated ECs displaying high proportion of ICAM-1 -cells (ECs-1) (greater than 50%) and non-activated ECs with low proportion of ICAM-1 -cells (ECs-2) (less than 25%). Only non-activated ECs-2 responded to SMG by elevating gene transcription and increasing ICAM-1 and VE-cadherin expression. This effect was enhanced after cumulative SMG-TNF-α exposure. ECs-1 displayed an unexpected decrease in number of E-selectin- and ICAM-1-positive ECs and pronounced up-regulation of VCAM1 upon activation of inflammation, which was partially abolished by SMG. Thus, non-activated ECs-2 are quite resistant to the impacts of microgravity and even exhibited an elevation of the VE-cadherin gene and protein expression, thus improving the integrity of the endothelial monolayer. Pre-activation of ECs with inflammatory stimuli may disturb the EC adhesion profile, attenuating its barrier function. These alterations may be among the mechanisms underlying cardiovascular dysregulation in real microgravity conditions.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%