Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C.
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.
Cooper
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Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, USA.
Pellis
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D000937:Antigen-Antibody Reactions; D019149:Bioreactors; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D008954:Models, Biological; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014893:Weightlessness
D016207:Cytokines; D007376:Interleukin-2; D015759:Ionomycin; D011493:Protein Kinase C