Inhibition of human lymphocyte proliferation and cleavage of interleukin-2 by Pseudomonas aeruginosa proteases.
This study was undertaken to determine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (ELA) on human lymphocyte function. AP at 50 micrograms/ml and ELA at 12 micrograms/ml caused a 50% inhibition of phytohemagglutinin-induced proliferation. There was no difference in the effect of proteases on CD4- and CD8-positive cells. To determine the effect of proteases on interleukin-2 (IL-2)-induced cell proliferation, the proteases and IL-2 were added to the IL-2-dependent CTLL-2 cell line. AP and ELA inhibited the proliferation of these cells. When IL-2 was added in excess, the inhibition was partly reversed. ELA at 10 micrograms/ml cleaved IL-2, as judged by size chromatography of a reaction mixture containing 125I-labeled IL-2 and the proteases. The ELA-digested IL-2 exhibited a reduced binding capacity to IL-2 receptors on the lymphocytes. Furthermore, treatment of phytohemagglutinin-stimulated lymphocytes with AP and ELA resulted in inhibition of binding of intact IL-2 to IL-2 receptors on the stimulated lymphocytes. These results indicated that P. aeruginosa-derived enzymes are able to interfere with human lymphocyte function in vitro and that this effect might be due to cleavage of IL-2.
D001667:Binding, Competitive; D010450:Endopeptidases / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000378:metabolism; D010196:Pancreatic Elastase / Q000494:pharmacology*; D010835:Phytohemagglutinins; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000276:immunology; D011971:Receptors, Immunologic / Q000187:drug effects; D015375:Receptors, Interleukin-2; D012697:Serine Endopeptidases
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D010450:Endopeptidases; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; C032923:microbial serine proteinases