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  • 1990-1994  (14)
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  • 1
    Publication Date: 2011-08-24
    Description: Spaceflight experiments since 1981 have demonstrated that certain cell functions are altered by micro-g. Biophysical models suggest that cell membranes and organelles should not be affected directly by gravity, however, the chemical microenvironment surrounding the cell and molecular transport could be altered by reduced gravity. Most experiments have used suspended live cells in small chambers without stirring or medium exchange. Flight results include increased attachment of anchorage-dependent human cells to collagen coated microcarriers, reduced secretion of growth hormone from pituitary cells, decreased mitogenic response of lymphocytes, increased Interferon-alpha by lymphocytes, increased Interleukin-1 and Tumor Necrosis Factor secretion by macrophages. Related experiments on cells immediately postflight and on procaryotic cells have shown significant changes in secretory capacity, cell proliferation, differentiation and development. Postulated mechanism include altered cell-cell interactions, altered calcium ion transport, effects on cell cytoskeleton, transport of transmitters and interactions with receptors. The discussion includes use of new molecular methods, considerations for cell environmental control and a preview of several experiments planned for the Shuttle and Spacelab flights to study the basic effects of microgravity on cellular physiology and potential interactions of spaceflight with radiation damage and cellular repair mechanisms.
    Keywords: Life Sciences (General)
    Type: The Physiologist (ISSN 0031-9376); Volume 35; 1 Suppl; S31-4
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  • 2
    Publication Date: 2011-08-24
    Description: Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.
    Keywords: Life Sciences (General)
    Type: Regional immunology (ISSN 0896-0623); Volume 4; 4; 236-44
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  • 3
    Publication Date: 2011-08-24
    Description: Experiments conducted on STS-50 indicated that space flight significantly inhibited tumor necrosis factor (TNF)-mediated killing of LM929 cells compared to ground controls. In ground-based studies, activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (PMA) also inhibited TNF-mediated killing of LM929 cells. Therefore, we used PKC inhibitors to determine if the inhibitory effects of spaceflight on TNF-mediated cytotoxicity involved the activation of PKC. In experiments conducted onboard space shuttle mission STS-54, we saw that in the presence of the protein kinase C inhibitors H7 and H8, TNF-mediated cytotoxicity was restored to levels of those observed in the ground controls. Subsequent experiments done during the STS-57 mission tested the dose response of two protein kinase inhibitors, H7 and HA1004. We again saw that killing was restored in a dose-dependent manner, with inhibitor concentrations known to inhibit PKC being most effective. These data suggest that space flight ameliorates the action of TNF by affecting PKC in target cells.
    Keywords: Life Sciences (General)
    Type: Experimental cell research (ISSN 0014-4827); Volume 211; 1; 171-4
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  • 4
    Publication Date: 2011-08-24
    Description: Class I and class II major histocompatibility complex (MHC) molecules play significant roles in T cell development and immune function. We show that MHCI- and MHCII-deficient mice have low numbers of macrophage precursors and circulating monocytes, as well as abnormal bone marrow cell colony-stimulating factor type 1 secretion and bone composition. We suggest that MHCI and MHCII molecules play a significant role in macrophage development.
    Keywords: Life Sciences (General)
    Type: Journal of leukocyte biology (ISSN 0741-5400); Volume 55; 5; 658-61
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  • 5
    Publication Date: 2011-08-24
    Description: We have identified three distinct cell phenotypes with respect to the conditions under which cells became susceptible to TNF-mediated lysis. These conditions include: 1) treatment with the protein synthesis inhibitor, cycloheximide; 2) contact with activated macrophages, and 3) infection with vaccinia virus. Whereas vaccinia virus-infected 3T3 cells became sensitive to soluble TNF, F5b cells required contact with activated macrophages. We showed that the "macrophage-resistant" F5m cells did not become sensitive to TNF or to killing by activated macrophages after infection with vaccinia virus. Therefore, vaccinia infection does not sensitize all cells to TNF. We also determined the pathways of lysis for cells after sensitization. Whereas 3T3, LM929, and F5b cells were killed by the process of necrosis, F5m cells lysis was characterized by the release of low mol wt DNA fragments (apoptosis).
    Keywords: Life Sciences (General)
    Type: Journal of leukocyte biology (ISSN 0741-5400); Volume 53; 1; 37-44
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  • 6
    Publication Date: 2011-08-24
    Description: We describe the use and appropriateness of antiorthostatic suspension in immunological investigations. This manuscript describes the model and discusses how well data obtained by using the model correlate with spaceflight data. This review concludes with some suggestions for future experiments using antiorthostatic suspension.
    Keywords: Aerospace Medicine
    Type: Journal of leukocyte biology (ISSN 0741-5400); Volume 54; 3; 227-35
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  • 7
    Publication Date: 2011-08-24
    Description: The tumor necrosis factor-alpha (TNF)-resistant, SV40-transformed, murine fibroblast cell lines, F5b and F5m, became sensitive to TNF-mediated cytolysis after treatment with a biologically active 18 kDa peptide fragment (SGP) derived from a 66-kDa parental cell surface sialoglycoprotein. Neither TNF nor the SGP alone exhibited cytotoxicity to the two SV40-transformed cell lines. However, Balb/c 3T3 cells, incubated with SGP alone or with SGP and TNF, were not killed. Therefore, SGP can selectively sensitize cells for TNF alpha-mediated cytotoxicity. This selective sensitization may be due to the previously documented ability of the SGP to selectively mediate cell cycle arrest.
    Keywords: Life Sciences (General)
    Type: Biochemical and biophysical research communications (ISSN 0006-291X); Volume 205; 1; 215-20
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  • 8
    Publication Date: 2019-07-13
    Description: We used major histocompatibility complex class II antigen-deficient transgenic mice to show that in vitro natural killer cell cytotoxicity and T-cell activation by staphylococcal exotoxins (superantigens) are not dependent upon the presence of major histocompatibility complex class II molecules. T cells can be activated by exotoxins in the presence of exogenously added interleukin 1 or 2 or in the presence of specific antibody without exogenously added cytokines.
    Keywords: Life Sciences (General)
    Type: Infection and immunity (ISSN 0019-9567); 61; 9; 4013-6
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  • 9
    Publication Date: 2019-08-15
    Description: This manuscript briefly reviews ground-based and flight experiments, discusses how those experiments complement each other, and details how those experiments lead us to speculate about the gravity-sensitive nature of protein kinase C.
    Keywords: Aerospace Medicine
    Type: Transactions of the Kansas Academy of Science (ISSN 0022-8443); 96; 2-Jan; 74-9
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  • 10
    Publication Date: 2019-08-15
    Description: Experiments were conducted to determine the effects of physiologically elevated corticosterone on the activation of macrophages and T cells. These studies find that the elevation of corticosterone does not affect the expression of membrane receptors on macrophages and does not affect the activation of macrophages to produce cytokines. In contrast, elevated corticosterone levels correlate with enhanced T cell proliferation to both mitogens and superantigens.
    Keywords: Life Sciences (General)
    Type: Transactions of the Kansas Academy of Science (ISSN 0022-8443); 95; 2-Jan; 23-8
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