The site of action of the Staphylococcus alpha toxin.

The present study concerns the site of action of the staphylococcus alpha toxin. This powerful necrotizing agent produced by pathogenic strains of staphylococcus is very probably important in the pathogenesis of localized staphylococcus disease and in the shock-like picture sometimes associated with staphylococcus septicemia. Our previous studies had suggested that the toxin has a selective effect on vascular smooth muscle. In investigating this problem further, the following observations were made. 1. The toxin produces an immediate hyperperistalsis and sustained increase in intraluminal tension progressing ultimately to atony and flaccid paralysis in the isolated smooth muscle preparation. 2. The addition of specific antitoxin prior to exposure to toxin prevents this reaction. However, when antitoxin is added after the toxin, no ameliorating effect is seen. 3. The toxin is rapidly and irreversibly bound to its substrate since washing the bowel segment 30 seconds after exposure to toxin fails to change the course of the reaction. 4. Vena caval segments exposed to toxin exhibit a similar initial rise in intraluminal tension followed by flaccid paralysis at which point they no longer respond to epinephrine stimulation. 5. When the toxin is infiltrated in the neighborhood of muscular blood vessels in the living rabbit selective necrosis of smooth muscle cells of the vessel walls is seen. 6. The selective effect on smooth muscle is emphasized by the failure of the toxin to affect the contractility of skeletal and cardiac muscle. 7. Perfusion of the isolated kidney and heart produces an increased resistance to flow after toxin is added to the perfusate. 8. Epithelial cells and fibroblasts in tissue culture exposed to high concentration of toxin for 2 hours are unaffected in their ability to recover and metabolise. This is in marked contrast to the effect on the smooth muscle preparation. The probability that the toxic effect on smooth muscle cells explains some of the local and systemic effects of staphylococcus infection is discussed.