Spaceflight alters immune cell function and distribution

Sonnenfeld, Gerald; Mandel, Adrian D.; Konstantinova, Irena; Berry, W. D.; Taylor, Gerald R.; Lesnyak, A. T.; Fuchs, Boris; Rakhmilevich, Alexander L.

doi:10.1152/jappl.1992.73.2.s191

Cited by 86 publications

(63 citation statements)

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“…The mechanisms underlying these abnormalities are unclear, but many immunological studies performed on astronauts postflight have described decreases in the number and function of circulating leukocytes, as well as a depressed proliferative response of in vitro mitogen-stimulated T cells (Taylor and Dardano, 1984;Meehan et al, 1992;Sonnenfeld et al, 1992;Stowe et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Effects of Simulated Microgravity on Primary Human NK Cells

Mei²,

Huyan³

et al. 2013

Astrobiology

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The deleterious effects of microgravity on lymphocytes have been demonstrated in previous studies. However, research on the effects of microgravity on human natural killer (NK) cells remains exceedingly limited. In this study, we demonstrated that NK cell cytotoxicity was significantly decreased under simulated microgravity (SMG) conditions ( p < 0.05). Several processes, including apoptosis, receptor expression, and cytokine secretion, were investigated in human NK cells under SMG. We observed decreased cytotoxicity, concurrent with increased apoptosis and necrosis, in NK cells after exposure to SMG ( p < 0.05). Additionally, interferon (IFN)-c and perforin expression decreased significantly, and the expression of granzyme-B was only slightly reduced. Meanwhile, SMG selectively inhibited the expression of certain surface receptors on NK cells. Specifically, the expression of NKG2A and NKG2D were significantly downregulated under SMG, but the expression of NKp30 and NKp44 was not affected. We also found that interleukin (IL)-15 alone or in combination with IL-12 could counteract the inhibition of NK cell cytotoxicity under SMG. Our findings indicate that human NK cells were sensitive to SMG, as reflected by their decreased cytotoxicity. Factors such as increased early apoptosis and late apoptosis/necrosis and the decreased expression of INF-c, cytolytic proteins, and cell surface receptors may be responsible for the loss of cytotoxicity in human NK cells under SMG. A combination of IL-12 and IL-15 may be useful as a therapeutic strategy for overcoming the effects of microgravity on human NK cells during long space missions.

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Section: Introductionmentioning

confidence: 99%

Effects of Simulated Microgravity on Primary Human NK Cells

Mei²,

Huyan³

et al. 2013

Astrobiology

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“…In this model, rodents are suspended by the tail, with a head-down tilt of 15-20° and with no load bearing on the hind limbs [2-4, 6-8, 11] . This exposure, which results in bone and muscle loss and fl uid shifts similar to those that occur during space fl ight, also induces changes in the immune system [1,[11][12][13][14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

“…Data obtained from several studies have increased our understanding of the complex interactions between the neuroendocrine and immune systems that occur during space fl ight [1,13,14,[17][18][19]52] . These interactions and the changes observed during space fl ight are probably the…”

Section: Introductionmentioning

confidence: 99%

Effects of Space Flight Conditions on the Function of the Immune System and Catecholamine Production Simulated in a Rodent Model of Hindlimb Unloading

Avilés

Belay

Vance

et al. 2005

Neuroimmunomodulation

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The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. Objective: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. Methods: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. Results: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. Conclusion: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections.

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“…Spaceflight is a stressful event that can affect the structural and functional parameters of the immune system [1][2][3][4][5]. Following spaceflight, thymic involution [6], inhibited lymphocyte blastogenesis [5,6], altered profiles of circulating leukocytes [7] and cytokine production [8], and depressed capacities of bone marrow cells to respond to colony stimulating factors [9] have been reported.…”

Section: Introductionmentioning

confidence: 99%

Antiorthostatic Suspension Stimulates Profiles of Macrophage Activation in Mice

Miller

Bates

Koebel

et al. 1999

Neuroimmunomodulation

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The antiorthostatic suspension model simulates certain physiological effects of spaceflight. We have previously reported BDF1 mice suspended by the tail in the antiorthostatic orientation for 4 days express high levels of resistance to virulent Listeria monocytogenesinfection. In the present study, we examined whether the increased resistance to this organism correlates with profiles of macrophage activation, given the role of the macrophage in killing this pathogen in vivo. We infected BDF1 mice with a lethal dose of virulent L. monocytogenes on day 4 of antiorthostatic suspension and 24 h later constructed profiles of macrophage activation. Viable listeria could not be detected in mice suspended in the antiorthostatic orientation 24 h after infection. Flow cytometric analysis revealed the numbers of granulocytes and mononuclear phagocytes in the spleen of infected mice were not significantly altered as a result of antiorthostatic suspension. Splenocytes from antiorthostatically suspended infected mice produced increased titers of IL-1. Serum levels of neopterin, a nucleotide metabolite secreted by activated macrophages, were enhanced in mice infected during antiorthostatic suspension, but not in antiorthostatically suspended naive mice. Splenic macrophages from mice infected on day 4 of suspension produced enhanced levels of lysozyme. In contrast to the results from antiorthostatically suspended infected mice, macrophages from antiorthostatically suspended uninfected mice did not express enhanced bactericidal activities. The collective results indicate that antiorthostatic suspension can stimulate profiles of macrophage activation which correlate with increased resistance to infection by certain classes of pathogenic bacteria.

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Spaceflight alters immune cell function and distribution

Cited by 86 publications

References 0 publications

Effects of Simulated Microgravity on Primary Human NK Cells

Effects of Simulated Microgravity on Primary Human NK Cells

Effects of Space Flight Conditions on the Function of the Immune System and Catecholamine Production Simulated in a Rodent Model of Hindlimb Unloading

Antiorthostatic Suspension Stimulates Profiles of Macrophage Activation in Mice

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