The influence of specific antibody on the disappearance of staphylococcal enterotoxin B from blood.

Abstract

Staphylococcus aureus produces a variety of toxins, enzymes, and metabolites, among which are enterotoxins A and B, exotoxins associated with certain outbreaks of food poisoning (2). Recent reports have established the lethal nature of enterotoxin B after its intravenous injection, with death in experimental animals characterized by profound shock (3-5). Fever and several other toxic manifestations of intravenously administered staphylococcal enterotoxin B (SEB) resemble those of bacterial endotoxin (6-10). In view of a possible etiologic relationship of staphylococcal enterotoxin to the shock syndrome of staphylococcal sepsis, there has been surprisingly little investigation of intravenously administered enterotoxin.The purified toxin produced by Schantz and coworkers (11) has been characterized extensively. It was shown to be a simple protein, free of any detectable lipid or carbohydrate, having a molecular weight of approximately 35,000. Electrophoretic studies revealed its migration as a single component with an isoelectric point of pH 8.6. Serologic studies by means of the Oudin and Ouchterlony techniques indicated greater than 99%o homogeneity. It will withstand a temperature of 60°C for 16 hours without loss of toxicity.Previous work performed in our laboratory showed that SEB was cleared rapidly from the blood of experimental animals (4). It was observed further that animals surviving an initial challenge appeared to clear SEB at a somewhat slower rate after a second challenge. In contrast, * Submitted for publication September 28, 1965; accepted May 23, 1966.A portion of this work appeared in abstract form (1). In conducting the research described in this report, the investigators adhered to the principles of laboratory animal care as established by the National Society for Medical Research. other investigators have shown that the phenomenon of tolerance and immunity to bacterial endotoxins are characterized by increased, rather than delayed, rates of clearance (12, 13). In view of certain similarities in the toxic manifestations of these two bacterial products it seemed paradoxical that a degree of immunity might alter their clearance kinetics in opposite directions.The present report extends observations on the clearance rate of labeled SEB from the circulation of rhesus monkeys and demonstrates the marked alterations in clearance rate produced by acutely administered type specific antitoxins. MethodsAnimals. Healthy Macaca mulatta (rhesus) weighing 2.5 to 3.5 kg were placed at least 1 week preceding investigation in restraining chairs 'specially designed to permit study in a nonanesthetized state. These animals had no known previous experience with SEB, and each was used for only a single challenge with this toxin. On the day before study bilateral indwelling saphenous vein catheters were inserted, one to permit injection of the test materials and the second to allow repeated blood sampling.Labeling and administration of toxin. The highly purified SEB as described by Schantz (11) was isotopically lab...

The Staphylococcal Enterotoxins

“…Evidence from various early animal models implicates the kidney in general, and renal proximal tubujkcells in particular, as the major target of SEB uptak^Morris et al, 1967;Rapoport et al, 1967;Normann et al, 1969). The SEB-induced death of rabbits can be prevented by nephrectomy after toxin administration.…”

“…The SEB-induced death of rabbits can be prevented by nephrectomy after toxin administration. The rapid clearance of I31 I-labelled SEB from the blood in Rhesus monkeys is retarded by renal artery ligation, but it is unaffected by the pharmacological blockade of the reticuloendothelial (phagocytic) system, suggesting that the enterotoxin is sequestered in the kidney epithelium (Rapoport et al, 1967). If [ 131 I]SEBAS administered intravenously to monkeys, 32% is localised to the kidney within 30 minutes, as determined by autopsy, and 97% of the radioactivity in the kidney is in the renal cortex, which is the site of proximal renal tubules (Morris et al, 1967k These observations are supported^, Anmunofluorescence studies, which showed that sequestration of fluorescein isothiocyanate (FITC)-labelled SEB in the kidney is prevented if glomerular filtration is interrupted by ligation of the ureters (Normann, 1971;Normann and Stone, 1972).…”

Effect of 5‐lipoxygenase inhibitor MK591 on early molecular and signaling events induced by staphylococcal enterotoxin B in human peripheral blood mononuclear cells

“…Evidence from experiments performed using animal models implicates the kidney in general, and the REPTCs in particular, as the major target of SEB uptake. It is also clear that 70% of injected SEB is accumulated in proximal tubule cells within 2 h [29–31] of stimulation. Based on the evidence of kidney involvement in blood pressure regulation, it is not unreasonable to hypothesize that damage to the renal epithelium caused by a vascular shock‐inducing agent, such as SEB (which possesses the ability to interact directly with the vascular tone‐regulating kidney cells), may contribute to the development of systemic shock (unpublished results).…”

Identification of Staphylococcal Enterotoxin B Domains Involved in Binding to Cultured Human Kidney Proximal Tubular Cells: Imparting Proliferation and Death

“…In vivo studies show that the clearance of 125 I-SEB is markedly altered by perturbations in renal blood flow (10,14). Other studies indicate that SEB is predominantly confined (more than 75% of the injected dose) to proximal tubular (PT) cells (11).…”