title: Toxic shock syndrome toxin-1 induces inositol phospholipid turnover, protein kinase C translocation, and calcium mobilization in human T cells.
abstract: Toxic shock syndrome toxin-1 (TSST-1) is a 22-kDa exotoxin produced by most Staphylococcus aureus strains responsible for toxic shock syndrome. TSST-1 is a mitogen for human T cells. The mechanism of T cell activation by TSST-1 was investigated. TSST-1 induced IL-2R expression, IL-2 synthesis, and proliferation in T cells in a monocyte-dependent fashion. Neither IL-1 nor IL-2, alone or in combination, substituted for monocytes in supporting TSST-1-induced mitogenesis. We investigated the mechanism by which TSST-1 induces initogenesis. TSST-1 failed to induce ADP-ribosylation of T cell membrane proteins. However, the toxin induced transient translocation of protein kinase C from cytosol to plasma membranes and also induced the mobilization of cellular Ca2+ stores in both PBMC and the Jurkat human tumor T cell line, suggesting that TSST-1 triggered inositol phospholipid turnover. This was directly demonstrated to be the case in both cellular preparations studied. TSST-1 induced the increased synthesis of the inositol phospholipid phosphatidyl inositol, phosphatidyl inositol-4 phosphate, and phosphoinositol inositol-4,5-bisphosphate, and induced the breakdown of inositol phospholipid as evidence by the accumulation of phosphatidic acid and inositol phosphates. We conclude that the action of TSST-1 involves the induction of inositol phospholipid turnover, protein kinase C activation, and mobilization of cellular Ca2+ stores. This effect is similar to that of mitogenic lectins and of anti-CD3 antibodies.
authors.affiliation: Division of Allergy/Immunology, Children's Hospital, Boston, MA.
authors.forename: T
authors.initials: T
authors.lastname: Chatila
authors.forename: N
authors.initials: N
authors.lastname: Wood
authors.forename: J
authors.initials: J
authors.lastname: Parsonnet
authors.forename: R S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000502:physiology; D001427:Bacterial Toxins; D001692:Biological Transport; D002051:Burkitt Lymphoma / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015375:Receptors, Interleukin-2; D018089:Superantigens; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D007375:Interleukin-1; D007376:Interleukin-2; D010716:Phosphatidylinositols; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D000246:Adenosine Diphosphate Ribose; D011493:Protein Kinase C; D002118:Calcium