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Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C
Author(s) -
Cooper David,
Pellis Neal R.
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.63.5.550
Subject(s) - ionomycin , biology , cd28 , peripheral blood mononuclear cell , protein kinase c , microbiology and biotechnology , secretion , signal transduction , cd3 , cell culture , t cell , immunology , antigen , biochemistry , immune system , intracellular , cd8 , in vitro , genetics
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. J. Leukoc. Biol . 63: 550–562; 1998.