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Published on: January 15, 2018
Medullasin enhances human natural killer cell activity
Abstract:
Medullasin, a new serine protease found in bone marrow cells, increased markedly human natural killer cell activity. Whereas the natural killer cell activity measured immediately after the treatment with medullasin remained almost on the same level as the control, an incubation at 37 degrees C for several hours increased markedly the natural killer cell activity of the lymphocytes treated with medullasin. Enhancement of the natural cytotoxicity was caused by the treatment with physiologic concentrations of the protease (5-20 micrograms/ml). Inhibitors of medullasin such as phenylmethylsulfonyl fluoride and elastatinal prevented the activation of natural cytotoxicity. Depletion of lymphocytes bearing Fc receptors for IgG abolished the enhancement of natural killer cell activity by medullasin. Interferon activity was not detected in the supernatant of lymphocyte cultures stimulated with medullasin. The medullasin enhanced further the natural killer cell activity of lymphocytes stimulated with interferon. Medullasin activity was detected neither in unstimulated nor stimulated (by concanavalin A or phytohemagglutinin) human lymphocytes. The protease was released easily from human mature granulocytes into culture medium. It is considered from these results that the level of human natural killer cell activity is regulated by medullasin released by mature granulocytes.
Insights
Medullasin, a novel serine protease, significantly boosts human natural killer cell activity after incubation. This protease, released by mature granulocytes, regulates natural killer cell function and enhances responses to interferon.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Natural killer (NK) cells are crucial for innate immunity.
- Regulation of NK cell activity is vital for immune response.
- Serine proteases play diverse roles in biological processes.
Purpose of the Study:
- To investigate the effect of medullasin on human natural killer cell activity.
- To elucidate the mechanism of medullasin-mediated NK cell activation.
- To determine the source and regulation of medullasin activity.
Main Methods:
- Treatment of human lymphocytes with purified medullasin.
- Assay of natural killer cell cytotoxicity.
- Inhibition studies using protease inhibitors.
- Flow cytometry to assess Fc receptor-bearing lymphocytes.
- Detection of interferon activity.
Main Results:
- Medullasin significantly enhanced NK cell activity following a 37°C incubation period.
- The enhancement was observed at physiological protease concentrations (5-20 µg/ml).
- Medullasin-induced activation was blocked by specific inhibitors and by depleting Fc receptor-bearing lymphocytes.
- Medullasin potentiated interferon-stimulated NK cell activity but did not induce interferon itself.
- Medullasin was released from mature granulocytes and was not detected in unstimulated or mitogen-stimulated lymphocytes.
Conclusions:
- Medullasin is a novel serine protease that activates human natural killer cells.
- NK cell activity regulation involves medullasin released by mature granulocytes.
- Medullasin represents a new target for modulating immune responses.
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