Effects of spaceflight and PEG-IL-2 on rat physiological and immunological responses

Chapes, Stephen K.; Simske, Steven J.; Sonnenfeld, Gerald; Miller, Edwin S.; Zimmerman, Robert J.

doi:10.1152/jappl.1999.86.6.2065

Cited by 55 publications

(40 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Decreases in the content and phytohemagglutinin reactivity of T cells, T cell cytotoxicity, and T cell helper activity have also been similarly reported Cooper and Pellis, 1998;Chapes et al, 1999]. This spectrum of immunological changes have also been confirmed in ground-based simulations of microgravity [Armstrong et al, 1993;Chapes et al, 1993;Cooper et al, 2001;Woods et al, 2003Woods et al, , 2005Boonyaratanakornkit et al, 2005;Ward et al, 2006;Wang et al, 2009].…”

supporting

confidence: 56%

“…Previous work has documented elevated corticosteroid levels resulting from spaceflight [Chapes et al, 1999;Stowe et al, 2003]. There is also evidence that glucocorticoids are involved in not only stress related apoptosis, but also play a role in T cell differentiation and death via the TCR trigger [Gruber et al, 1994;Penninger and Kroemer, 1998].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors

Lebsack

Woods

et al. 2010

J of Cellular Biochemistry

View full text Add to dashboard Cite

The detrimental effects of spaceflight and simulated microgravity on the immune system have been extensively documented. We report here microarray gene expression analysis, in concert with quantitative RT-PCR, in young adult C57BL/6NTac mice at 8 weeks of age after exposure to spaceflight aboard the space shuttle (STS-118) for a period of 13 days. Upon conclusion of the mission, thymus lobes were extracted from space flown mice (FLT) as well as age- and sex-matched ground control mice similarly housed in animal enclosure modules (AEM). mRNA was extracted and an automated array analysis for gene expression was performed. Examination of the microarray data revealed 970 individual probes that had a 1.5-fold or greater change. When these data were averaged (n = 4), we identified 12 genes that were significantly up- or down-regulated by at least 1.5-fold after spaceflight (P < or = 0.05). The genes that significantly differed from the AEM controls and that were also confirmed via QRT-PCR were as follows: Rbm3 (up-regulated) and Hsph110, Hsp90aa1, Cxcl10, Stip1, Fkbp4 (down-regulated). QRT-PCR confirmed the microarray results and demonstrated additional gene expression alteration in other T cell related genes, including: Ctla-4, IFN-alpha2a (up-regulated) and CD44 (down-regulated). Together, these data demonstrate that spaceflight induces significant changes in the thymic mRNA expression of genes that regulate stress, glucocorticoid receptor metabolism, and T cell signaling activity. These data explain, in part, the reported systemic compromise of the immune system after exposure to the microgravity of space.

show abstract

supporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors

Lebsack

Woods

et al. 2010

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…The results in regard to thymus mass are more variable because thymus mass has been reported to decrease16, increase18 or remain unchanged compared to controls192021. Observed reductions in spleen and thymus mass are often explained by a stress response2223.…”

Section: Discussionmentioning

confidence: 99%

Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

Ghislin

Ouzren-Zarhloul

Kaminski

et al. 2015

Sci Rep

View full text Add to dashboard Cite

During spaceflight, organisms are subjected to mechanical force changes (gravity (G) changes) that affect the immune system. However, gravitational effects on lymphopoiesis have rarely been studied. Consequently, we investigated whether the TCRβ repertoire, created by V(D)J recombination during T lymphopoiesis, is affected by hypergravity exposure during murine development. To address this question, C57BL/6j mice were mated in a centrifuge so that embryonic development, birth and TCRβ rearrangements occurred at 2G. Pups were sacrificed at birth, and their thymus used to quantify transcripts coding for factors required for V(D)J recombination and T lymphopoiesis. We also created cDNA mini-libraries of TCRβ transcripts to study the impact of hypergravity on TCRβ diversity. Our data show that hypergravity exposure increases the transcription of TCRβ chains, and of genes whose products are involved in TCR signaling, and affects the V(D)J recombination process. We also observed that ~85% of the TCRβ repertoire is different between hypergravity and control pups. These data indicate that changing a mechanical force (the gravity) during ontogeny will likely affect host immunity because properties of loops constituting TCR antigen-binding sites are modified in hypergravity newborns. The spectrum of peptides recognized by TCR will therefore likely be different.

show abstract

“…The increased expression of IL-8, a chemoattractant for neutrophils, results in increased demargination of the neutrophils. Chapes et al (5) observed monocytopenia in rats aboard a shuttle mission lasting 8 days. Resident macrophages of these rats secreted higher TNF-␣ levels in response to LPS and staphylococcal enterotoxin B compared to the ground controls.…”

Section: Discussionmentioning

confidence: 99%

Effect of Spaceflight on Ability of Monocytes To Respond to Endotoxins of Gram-Negative Bacteria

Kaur

Simons

Kapadia

et al. 2008

Clin Vaccine Immunol

View full text Add to dashboard Cite

Astronauts live and work in relatively crowded, confined environments on the Space Shuttle and the International Space Station. They experience a unique set of stressors that contribute to a diminishment of many immune responses. This study investigated the ability of the shuttle crew members' monocytes to respond to gram-negative endotoxin that they could encounter during infections. Blood specimens were collected from 20 crew members and 15 control subjects 10 days before launch, 3 to 4 h after landing, and 15 days after landing and from crew members during their annual medical examination at 6 to 12 months after landing. When challenged with gram-negative endotoxin, the crew member's monocytes collected at all three time points produced lower levels of interleukin-6 (IL-6) and IL-1␤ and higher levels of IL-1ra and IL-8 compared to those of control subjects. Cytokines were assessed by measuring the number of cells positive for intracellular cytokines. These values returned to normal 6 to 12 months after landing, except for IL-1ra, which was still higher (five-to sixfold) than in controls. This phenomenon was accompanied by an increased expression of Toll-like receptor 4 and decreased expression of CD14 on the crew members' monocytes at all time points. There were also increased levels of the lipopolysaccharide binding protein in the plasma of the crew members 3 to 4 h and 15 days after landing. This study shows that spaceflight-associated factors (in-flight and preflight) modulate the response of monocytes to gram-negative endotoxins.During spaceflight, astronauts are affected by many unusual factors, such as microgravity, radiation, physical and mental stresses, and isolation. Not only is spaceflight associated with in-flight factors influencing the astronauts, but even before launch, in preparation for the mission, the astronauts experience changes in circadian rhythms, rigorous training, and stresses of anticipation factors. Additionally, confinement of the crew during flight can and has resulted in the transfer of microorganisms between crew members (13,26,27). All of these factors are known to affect many physiological parameters of the astronauts, including the immune system (12,17,20,31,32,41). Their effects include decreased functions of cells of the innate immune system, including neutrophils (14, 36), monocytes (15), and NK cells (17,21). The innate immune system initiates the host defense against invading microbes by specific recognition mechanisms. The family of Toll-like receptors (TLRs) on monocytes have been shown to be involved in innate immune recognition in response to microbial antigens (1, 6, 38), such as lipopolysaccharide (LPS), or endotoxin, a major virulence factor of gram-negative bacteria (29). Tapping et al. (39) have shown that TLR4 is the predominant signaling receptor for LPS in human blood. In blood, LPS binds to LPS binding protein (LBP), which facilitates the transfer of LPS to CD14 molecules in the CD14-TLR4-MD2 complex on the cell membrane of monocytes (11). CD14 plays a ke...

show abstract

Effects of spaceflight and PEG-IL-2 on rat physiological and immunological responses

Cited by 55 publications

References 47 publications

Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors

Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors

Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

Effect of Spaceflight on Ability of Monocytes To Respond to Endotoxins of Gram-Negative Bacteria

Contact Info

Product

Resources

About