Cytokine secretion by immune cells in space

Chapes, Stephen K.; Morrison, Dennis R.; Guikema, James A.; Lewis, Marian L.; Spooner, Brian S.

doi:10.1002/jlb.52.1.104

Cited by 80 publications

(31 citation statements)

References 17 publications

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“…In fact, the levels of these cytokines were increased. Increased secretion of these cytokines has been seen previously in cells exposed to microgravity in orbit [42,43] and may reflect a cellular response to stress. The increased levels of IL-1␤ and IL-6 in the PHA-RWV cultures could also indicate reduced uptake of these cytokines by receptors on the T cells.…”

Section: Discussionsupporting

confidence: 62%

Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C

Cooper

Pellis

1998

Journal of Leukocyte Biology

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Utilizing clinostatic rotating wall vessel (RWV) bioreactors that simulate aspects of microgravity, we found phytohemagglutinin (PHA) responsiveness to be almost completely diminished. Activation marker expression was significantly reduced in RWV cultures. Furthermore, cytokine secretion profiles suggested that monocytes are not as adversely affected by simulated microgravity as T cells. Reduced cell-cell and cell-substratum interactions may play a role in the loss of PHA responsiveness because placing peripheral blood mononuclear cells (PBMC) within small collagen beads did partially restore PHA responsiveness. However, activation of purified T cells with cross-linked CD2/CD28 and CD3/CD28 antibody pairs was completely suppressed in the RWV, suggesting a defect in signal transduction. Activation of purified T cells with PMA and ionomycin was unaffected by RWV culture. Furthermore, sub-mitogenic doses of PMA alone but not ionomycin alone restored PHA responsiveness of PBMC in RWV culture. Thus our data indicate that during polyclonal activation the signaling pathways upstream of PKC activation are sensitive to simulated microgravity.

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Section: Discussionsupporting

confidence: 62%

Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C

Cooper

Pellis

1998

Journal of Leukocyte Biology

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“…Therefore, the full model of space flight conditions was required to change interferon production and the stress of restraint was not sufficient to allow decreased in interferon production to develop [18]. Similar results were observed with interferon-γ production [19,20].…”

Section: Ground-based Model Studiessupporting

confidence: 60%

The Immune System in Space, Including Earth-Based Benefits of Space- Based Research

Sonnenfeld¹

2005

CPB

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Exposure to space flight conditions has been shown to result in alterations in immune responses. Changes in immune responses of humans and experimental animals have been shown to be altered during and after space flight of humans and experimental animals or cell cultures of lymphoid cells. Exposure of subjects to ground-based models of space flight conditions, such as hindlimb unloading of rodents or chronic bed rest of humans, has also resulted in changes in the immune system. The relationship of these changes to compromised resistance to infection or tumors in space flight has not been fully established, but results from model systems suggest that alterations in the immune system that occur in space flight conditions may be related to decreases in resistance to infection. The establishment of such a relationship could lead to the development of countermeasures that could prevent or ameliorate any compromises in resistance to infection resulting from exposure to space flight conditions. An understanding of the mechanisms of space flight conditions effects on the immune response and development of countermeasures to prevent them could contribute to the development of treatments for compromised immunity on earth.

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“…They secreted little to no TNF or NO in response to all agonists tried. This was in contrast to B6MPI02 (8,12) and wildtype peritoneal macrophages (8,12) that secrete TNF and NO in response to exotoxins and LPS. Nevertheless, the inability of C2D or C2Dt cells to secrete TNF in response to superantigens would be consistent with the poor responses of MHCIl-negative peritoneal macrophages (4).…”

Section: -contrasting

confidence: 55%

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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Cytokine secretion by immune cells in space

Cited by 80 publications

References 17 publications

Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C

Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C

The Immune System in Space, Including Earth-Based Benefits of Space- Based Research

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

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