STIMULATION OF HUMAN-LYMPHOCYTES BY CATHEPSIN-G

We investigated the effect of cathepsin G, a serine protease in polymorphonuclear granulocytes, on the function of human lymphocytes. Cathepsin G increased the [H-3]thymidine incorporation into human lymphocytes. This mitogenic activity was due to the proteolytic activity of cathepsin G. Both B and T cells showed increased [H-3]thymidine incorporation, and this effect was more remarkable for T cells than for B cells. Among the T cell subsets, CD4(+) T cells showed the increase in DNA synthesis, but CD8(+) T cells did not. When human lymphocytes were stimulated with cathepsin G, intracellular free Ca2+ concentration ([Ca2+](i)) increased in B and T cells, including CD4(+) T cells and CD8(+) T cells. The change in intracellular Ca2+ was due to Ca2+ influx and release of intracellular stores. Cathepsin G also induced the production of inositol 1,4,5-trisphosphate (IP3) in B cells, CD4(+) T cells, and CD8(+) T cells, leading to the release of Ca2+ from intracellular stores. Moreover, the stimulation with cathepsin G resulted in alkalization of the cytosol of B cells, CD4(+) T cells, and CD8(+) T cells as the result of Na+/H+ antiport activation. The change in intracellular Ca2+, production of IP3, and cytoplasmic alkalization in lymphocytes were due to its proteolytic activity. Cathepsin G released from granulocytes is considered to act on human lymphocytes in vivo and lead to the increase in DNA synthesis of B cells and CD4(+) T cells through IP3 production, an increase in [Ca2+](i), and alkalization. However, these second messengers do not lead to the increase in DNA synthesis of CD8(+) T cells. (C) 1995 Academic Press, Inc.