Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. V. Evidence that manganese inhibits a calcium-dependent step in programming for lysis |
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Authors: | M K Gately E Martz |
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Institution: | Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115 U.S.A. |
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Abstract: | The mechanism of T-lymphocyte-mediated cytolysis consists of three successive steps: adhesion formation, programming for lysis, and killer-cell-independent lysis. Mg2+, but not Ca2+, is required for adhesion formation, whereas programming for lysis is strongly Ca2+ dependent. We have previously reported that the transition metal manganese can substitute for Mg2+ in supporting adhesion formation. In the present paper, we demonstrate that manganese inhibits programming for lysis. The inhibitory effect of Mn2+ on cytolysis can be reduced by increasing the concentration of Ca2+. Furthermore, inhibitor sequencing experiments were unable to distinguish the step blocked by Mn2+ from the Ca2+-dependent step. These results suggest that Mn2+ blocks a Ca2+-dependent step(s) in programming for lysis. Present evidence does not distinguish whether the action of Ca2+ in programming for lysis is via a Ca2+ influx (as a “second messenger?”) or whether Ca2+ simply serves as a cofactor at the cell exterior. |
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Keywords: | Present address to which correspondence should be sent: Department of Microbiology University of Massachusetts Amherst Mass 01003 |
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