The mechanism of activation of human natural killer cells by medullasin.

Medullasin, a serine protease in granulocytes, has been shown to stimulate human natural killer cell activity through its proteolytic activity, without interferon induction. The protease is considered to exert its effect directly on large granular lymphocytes, because firstly the extent of activation of natural killer cell activity by medullasin was the same between peripheral blood lymphocytes and purified large granular lymphocytes, and secondly, addition of medullasin-treated lymphocyte fractions containing few large granular lymphocytes to the large granular lymphocyte fraction failed to enhance the natural killer cell activity of that fraction. Studies employing inhibitors of DNA, RNA and protein synthesis showed that both RNA and protein synthesis, but not DNA synthesis of lymphocytes are necessary for the enhancement of natural killer cell activity by medullasin. These results indicate that medullasin in granulocytes enhances the natural killer cell activity by directly stimulating large granular lymphocytes to induce certain protein(s).