Induction of CC chemokines in human peripheral blood mononuclear cells by staphylococcal exotoxins and its prevention by pentoxifylline.
We investigated the inflammatory processes that might be associated with the arthrogenic activity of Staphylococcus aureus, the principal causative agent of bacterial arthritis. Human peripheral blood mononuclear cells (PBMC) were stimulated with the staphylococcal toxic shock syndrome toxin-1 (TSST-1) or enterotoxin B (SEB) and the production of chemokines was examined. Both TSST-1 and SEB induced high levels (ng/mL) of MIP-1alpha, MIP-1beta, and MCP-1. The induction of these chemokines occurred mostly by direct stimulation of PBMC with staphylococcal exotoxins (SE), without requiring the intervention of IL-1 and TNF-alpha. The production of SE-induced chemokines was blocked partially by anti-DR and anti-CD2 antibodies. Cell separation revealed monocytes as the cell source of these chemokines. However, addition of purified T cells amplified the levels of chemokine produced, suggesting that cognate interaction of SE bound on antigen-presenting cells with T cells also contributes to chemokine production. The activation and recruitment of leukocytes by these chemokines may contribute to the pathophysiology of septic arthritis caused by staphylococci in humans through tissue injury and the recruitment of T lymphocytes, perhaps also initiating autoimmune responses. Pentoxifylline, an anti-inflammatory agent, completely inhibited the production of these chemokines.
Krakauer
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Department of Immunology and Molecular Biology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA.
D001427:Bacterial Toxins; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009000:Monocytes / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D001427:Bacterial Toxins; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D004768:Enterotoxins; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal; D010431:Pentoxifylline