Interleukin-1 stimulates diacylglycerol production in T lymphocytes by a novel mechanism.
We have investigated the biochemical mechanism by which interleukin-1 (IL-1) serves as a comitogen with agents that directly activate the antigen receptor in T lymphocytes. We have studied the human T cell line Jurkat, which can be stimulated to produce Interleukin-2 by treatment with antibodies that bind to the CD3-antigen receptor complex and hence represents a model system for T cell activation. Using highly purified, recombinant human IL-1, we show that IL-1 stimulates rapid diacylglycerol and phosphorylcholine production from phosphatidylcholine (PC) in the absence of phosphatidylinositol turnover in Jurkat cells. This effect is also observed in peripheral blood T cells and a murine T cell line. The EC50 for IL-1 was 28 fM, and PC hydrolysis was detectable within 5 sec at 37 degrees C. The murine cell line had typical high-affinity IL-1 receptors (kd = 7 X 10(-11) M). However, we were unable to detect IL-1 binding to Jurkat cells. This reaction occurs via a novel mechanism and may explain the comitogenic activity of IL-1 in T lymphocyte activation as well as many of the pleiotropic biologic effects of this cytokine.
D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D006800:Deltaretrovirus Infections; D004075:Diglycerides / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005989:Glycerides / Q000096:biosynthesis*; D006801:Humans; D006868:Hydrolysis; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation; D009829:Oleic Acids / Q000032:analysis; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013229:Stearic Acids / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D004075:Diglycerides; D005989:Glycerides; D007375:Interleukin-1; D009829:Oleic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D011994:Recombinant Proteins; D013229:Stearic Acids; D010767:Phosphorylcholine; D002118:Calcium