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 [3H]thymidine incorporation into human lymphocytes. This mitogenic activity was due to the proteolytic activity of cathepsin G. Both B and T cells showed increased [3H]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.
Department of Biochemistry and Nutrition, Institute of Public Health, Tokyo, Japan.
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Hase-Yamazaki
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Aoki
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D056649:Cathepsin G; D002403:Cathepsins / Q000502:physiology*; D002478:Cells, Cultured; D016257:Fura-2 / Q000031:analogs & derivatives; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D012697:Serine Endopeptidases; D013601:T-Lymphocytes / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D013729:Terpenes; C049925:fura-2-am; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D002118:Calcium; D016257:Fura-2