Nonpurulent response to toxic shock syndrome toxin 1-producing Staphylococcus aureus. Relationship to toxin-stimulated production of tumor necrosis factor.
Infection of surgical wounds with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus does not usually elicit a purulent response from the host. Because S. aureus is normally a pyogenic pathogen, this phenomenon suggests that strains of staphylococci that produce the exotoxin are able to inhibit the migration of polymorphonuclear neutrophils (PMN) to sites of infection. We have considered that inhibition of leukocyte migration may be an effect of secreted TSST-1 and have studied direct and indirect effects of the exotoxin on migratory functions of PMN in vitro. Preincubation of PMN with TSST-1 produced no inhibition of random motility or FMLP- or C5a-stimulated chemotaxis under agarose. Supernatant fluids from mononuclear leukocytes incubated with TSST-1, however, were potently inhibitory for both PMN random and chemotactic migratory functions. The inhibitor of migration was identified as TNF based upon neutralization by anti-TNF antiserum and its presence in the culture supernatant fluids assayed in terms of cytotoxicity for murine TNF-sensitive L-929 cell line cells. Preincubation of PMN with recombinant human TNF also inhibited subsequent PMN random and chemotactic migratory functions. We propose that TSST-1 inhibits the mobilization of PMN to sites of infection by stimulation of monocyte/macrophage TNF production and suggest that TNF may also contribute to some other effects of toxic shock syndrome.
Fast
D J
DJ
Department of Microbiology, University of Minnesota, Minneapolis 55455.
Schlievert
P M
PM
Nelson
R D
RD
D000818:Animals; D001427:Bacterial Toxins; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism; D018089:Superantigens; D013530:Surgical Wound Infection / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal