Skeletal unloading causes organ-specific changes in immune cell responses

Armstrong, Jason W.; Nelson, Karen; Simske, Steve; Luttges, Marvin W.; Iandolo, John J.; Chapes, Stephen K.

doi:10.1152/jappl.1993.75.6.2734

Cited by 43 publications

(24 citation statements)

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“…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%

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

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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.

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supporting

confidence: 56%

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

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“…The hindlimb unloading model has been adapted for use on mice to study the metabolic and immune responses of mice to antiorthostasis (3,4,8,40), as well as the musculoskeletal responses to unloading (36)(37)(38). With the increasing availability of transgenic and mutant strains of mice, the hindlimb unloading model is now being used to unravel molecular mechanisms that mediate responses to hindlimb unloading and antiorthostasis (10,24,28,44).…”

Section: Extension Of the System To Micementioning

confidence: 99%

Hindlimb unloading rodent model: technical aspects

Morey-Holton

Globus

2002

Journal of Applied Physiology

797

638

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Since its inception at the National Aeronautics and Space Administration (NASA) Ames Research Center in the mid-1970s, many laboratories around the world have used the rat hindlimb unloading model to simulate weightlessness and to study various aspects of musculoskeletal loading. In this model, the hindlimbs of rodents are elevated to produce a 30° head-down tilt, which results in a cephalad fluid shift and avoids weightbearing by the hindquarters. Although several reviews have described scientific results obtained with this model, this is the first review to focus on the technical aspects of hindlimb unloading. This review includes a history of the technique, a brief comparison with spaceflight data, technical details, extension of the model to mice, and other important technical considerations (e.g., housing, room temperature, unloading angle, the potential need for multiple control groups, age, body weight, the use of the forelimb tissues as internal controls, and when to remove animals from experiments). This paper is intended as a reference for researchers, reviewers of manuscripts, and institutional animal care and use committees. Over 800 references, related to the hindlimb unloading model, can be accessed via the electronic version of this article.

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“…Cells were evaluated for the expression of Mac-l, Mac-2, Thy 1, MHC I, and MHCII antigens using flow cytometry as described previously (2,3). Single cell suspensions of C2D, C2Dt, or B6MP102 ceils were incubated with primary antibody [Y-3, anti-K b (a generous gift from Dr. David Lee, University of Missouri, Columbia) or hybridoma HB-183 (ATCC) derived anti I-A and fluoreseeinated secondary antibody [F(ab')2; Cappel, Durham, NC] for 30 min, washed three times, and analyzed on a FACScan flow cytometer (BectonDickinson, Sunnyvale, CA).…”

Section: Methodsmentioning

confidence: 99%

Macrophage cell lines derived from major histocompatibility complex II-negative mice

Beharka

Armstrong

Chapes

1998

In Vitro Cell.Dev.Biol.-Animal

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Two bone-marrow-derived macrophage cell lines, C2D and C2Dt, were isolated from major histocompatibility class II negative knock-out mice. The C2D cell line was stabilized by continuous culture in colony-stimulating factor-1 and the C2Dt cell line was transformed with SV40 virus large T antigen. These cells exhibited phenotypic properties of macrophages including morphology and expression of Mac 1 and Mac 2 cell surface molecules. These cells also had comparable growth to the bone-marrow-derived macrophage cell line B6MP102. These new cell lines were not spontaneously cytotoxic and were only capable of modest killing of F5b tumor cells when stimulated with LPS and interferon-gamma, but not when stimulated with LPS alone or with staphylococcal exotoxin. C2D and C2Dt cells phagocytosed labeled Staphylococcus aureus similarly to B6MP102 cells but less well than C2D peritoneal macrophages. These cell lines secreted interleukin-6, but not tumor necrosis factor or nitric oxide in response to LPS or staphlococcal enterotoxins A or B C2D(t) cells were tumorigenic in C2D and C57BL/6J mice but C2D cells were not. These data suggest that macrophage cell lines can be established from bone marrow cells of major histocompatibility complex II-negative mice.

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Skeletal unloading causes organ-specific changes in immune cell responses

Cited by 43 publications

References 0 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

Hindlimb unloading rodent model: technical aspects

Macrophage cell lines derived from major histocompatibility complex II-negative mice

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