The staphylococcal enterotoxin serotype B (SEB)-induced enteric intoxication and the immediate-type reaction in the skin of unsensitized monkeys was used to define whether agents competing with SEB for target cell receptors may inhibit pathophysiological effects. For this purpose a duodenal provocation test was developed by use of a pediatric gastroscope, allowing the evaluation of the influence of antagonists on the intestinal disorder upon SEB challenge at the same duodenal site. First, carboxymethylation of histidine residues of SEB caused a complete loss of emetic and skinsensitizing activity without changing the immunological specificity. However, carboxymethylated SEB is a strong inhibitor of enteric intoxications and immediate-type skin reactions upon SEB challenge. Second, after immunization of BALB/c mice with monoclonal anti-SEB antibodies, monoclonal antiidiotypic antibodies (anti-Id) were obtained by the "hybridoma technique" and purification by idiotype-affinity chromatography. Anti-Id specifically inhibited the binding of horseradish peroxidase-labeled anti-SEB to the ligand, and SEB blocked as well the interaction of these two antibody species, indicating a high degree of binding-site selectivity. Anti-Id completely protected against emetic response and diarrhea upon duodenal provocation with SEB and inhibited immediate-type skin reactions as well. Further, anti-Id acted as an antagonist without triggering biologic functions themselves. This shows that anti-Id constitute a useful tool to protect against a bacterial toxininduced intestinal disorder.Staphylococcal enterotoxins (SE) are responsible for one of the most common types of food poisoning in humans (1). All SE produce emesis and diarrhea in humans and other primates as a result of oral administration, whereas the toxin appears to have little, if any, clinical effect in other laboratory animals (1). Although considerable efforts have been expended on attempts to define the pathogenesis, so far very little information has been available on the mode and cellular site of SE action in the gastrointestinal tract.Recently, however, evidence was provided that unsensitized monkeys develop an immediate-type reaction in the skin upon intradermal challenge with SE serotype B (SEB; ref.2). As shown by a series of experiments, SEB administered intradermally causes skin reactions by affecting mast cells (2). This type of nonimmunological mast cell stimulation by SEB offered a new approach, providing a model for investigating the mechanisms of SEB action. In addition, evidence was provided that carboxymethylation of SEB resulted in a loss of toxicity associated with the complete abrogation of skin-sensitizing activity without changing the immunological specificity of the toxin. It has been established that carboxymethylated SEB (CM-SEB) could compete with SEB for binding sites on the target-cell surface (2). To define whether SEB exerts its effect on mast cells by binding to specific celt-surface receptors or whether a less specific type of ligand-...
The staphylococcal enterotoxin B (SEB)-induced immediate-type skin reaction in unsensitized monkeys was used as a nonimmunological mast cell stimulus to examine whether the toxin exerts its effect via specific receptors on the target cell membrane. Anti-idiotypic antibodies (anti-Id) were raised in BALB/c mice against monoclonal anti-SEB antibodies (anti-SEB) and purified by idiotype affinity chromatography. The anti-Id nature of the antibody was demonstrated by its ability to inhibit the binding of 125I-labeled anti-SEB to the ligand in a concentration-dependent manner. Moreover, binding of anti-SEB to anti-Id was antagonized by the SEB ligand in a competitive way. These antibodies completely abolished skin reactions in unsensitized monkeys on challenge with SEB and impeded those provoked by staphylococcal enterotoxins A and C1 but did not have the biological activity of the toxin. These data are compatible with the view that receptors for staphylococcal enterotoxins may exist on the membrane of mast cells in the skin of unsensitized monkeys. The data suggest an experimental approach for producing anti-cell receptor antibodies that are of potential value to influence the course of staphylococcal enterotoxin-mediated effects.Staphylococcal enterotoxin has been implicated in one of the most prevalent types of food-borne debilitating enteric intoxication in humans. Next to man, monkeys are found to be the most susceptible to oral administration ofthe enterotoxin, which produces emesis and diarrhea, the classic symptoms of such food poisoning, whereas the toxin appears to have little clinical effect in other laboratory animals (1).Although considerable effort has been expended on attempts to clarify the pathogenesis, very little, if any, information was available on the mode and cellular site of staphylococcal enterotoxin action in the gastrointestinal tract (2).Recently, however, detailed evidence was provided that staphylococcal enterotoxin B (SEB) causes, in addition to emesis, immediate-type skin reactions in unsensitized monkeys by affecting cutaneous mast cells. That mast cell mediators are involved is reflected by the fact that both the skin reactions and the emetic responses to SEB are completely abolished by histamine H2 receptor antagonists and calcium channel blockers (3). Another feature of this study was the loss of toxicity associated with the complete abrogation of skin-sensitizing activity without changing the immunological specificity of SEB after carboxymethylation of the toxin. Furthermore it has been established that carboxymethylated SEB can in fact specifically inhibit the response to native SEB in unsensitized skin sites. Thus, it is reasonable to assume that carboxymethylated SEB competitively antagonizes the action of native SEB on binding sites of mast cells but is incapable of promoting activation signals by itself. It has to be delineated, however, whether SEB exerts its effect on mast cells by binding to specific cellsurface receptors or whether some less-specific type of ligand...
The immediate-type skin reaction in unsensitized monkeys upon challenge with staphylococcal enterotoxin B (SEB) was studied to define the role of mast cell receptors in the action of the toxin. For this purpose anti-idiotypic antibodies (anti-Id) were raised in BALB/c mice against monoclonal anti-SEB antibodies and purified by idiotype affinity chromatography. Anti-Id completely abolished skin reactions upon challenge with SEB without having biological functions itself. The data are compatible with the view that receptors for staphylococcal enterotoxin actually exist on the mast cell membrane of primates and anti-Id may be of potential value to influence the course of staphylococcal enterotoxin-mediated effects.
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