Streptococcal pyrogenic exotoxin F (SpeF) causes permeabilization of lung blood vessels

Acute respiration distress syndrome (ARDS) is a typical complication in tox ic shock-like syndrome (TSLS) caused by Streptococcus pyogenes. An isolated perfused rat lung model was used to identify the causative agent of ARDS i n TSLS in this study. Some crude preparations separated from the culture su pernatants of S. pyogenes isolates caused rapid increases in the weight of perfused lungs, indicating vascular permeabilization. Six samples from M ty pe 1 and 3 isolates from TSLS and pharyngitis patients showed strong permea bilization activity, whereas preparations from isolates of other M types (a lthough the number of isolates examined was limited) were negative, The act ive substance was purified to a single band by sodium dodecyl sulfate-polya crylamide gel electrophoresis using various columns, and the N-terminal ami no acid sequence was determined. The resultant sequence of eight amino acid s was identical to SpeF (mitogenic factor). Moreover, the vascular permeabi lization activity of the purified band was abolished with anti-SpeF antiser um prepared by immunizing with the purified SpeF, This activity was also ne utralized by the antiserum prepared by immunizing with a synthetic peptide derived from the published SpeF sequence. These results suggested that stre ptococcal SpeF is a major cause of permeabilization of lung blood vessels a nd sufficient for the pathogenesis of ARDS under the conditions of TSLS cau sed by S. pyogenes.