Matsumoto M, Ishikawa N, Saito M, Shibayama K, Horii T, Sato K, Ohta M
Department of Bacteriology, Nagoya University School of Medicine, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Infect Immun. 1999 Sep;67(9):4307-11. doi: 10.1128/IAI.67.9.4307-4311.1999.
Acute respiration distress syndrome (ARDS) is a typical complication in toxic shock-like syndrome (TSLS) caused by Streptococcus pyogenes. An isolated perfused rat lung model was used to identify the causative agent of ARDS in TSLS in this study. Some crude preparations separated from the culture supernatants of S. pyogenes isolates caused rapid increases in the weight of perfused lungs, indicating vascular permeabilization. Six samples from M type 1 and 3 isolates from TSLS and pharyngitis patients showed strong permeabilization activity, whereas preparations from isolates of other M types (although the number of isolates examined was limited) were negative. The active substance was purified to a single band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis using various columns, and the N-terminal amino acid sequence was determined. The resultant sequence of eight amino acids was identical to SpeF (mitogenic factor). Moreover, the vascular permeabilization activity of the purified band was abolished with anti-SpeF antiserum prepared by immunizing with the purified SpeF. This activity was also neutralized by the antiserum prepared by immunizing with a synthetic peptide derived from the published SpeF sequence. These results suggested that streptococcal SpeF is a major cause of permeabilization of lung blood vessels and sufficient for the pathogenesis of ARDS under the conditions of TSLS caused by S. pyogenes.
急性呼吸窘迫综合征（ARDS）是由化脓性链球菌引起的中毒性休克样综合征（TSLS）中的一种典型并发症。在本研究中，使用离体灌注大鼠肺模型来确定TSLS中ARDS的病原体。从化脓性链球菌分离株的培养上清液中分离出的一些粗制品导致灌注肺重量迅速增加，表明血管通透性增加。来自TSLS和咽炎患者的M1型和M3型分离株的六个样品显示出很强的通透性活性，而来自其他M型分离株的制品（尽管所检测的分离株数量有限）则为阴性。通过使用各种柱的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳将活性物质纯化至单一条带，并测定其N端氨基酸序列。所得的八个氨基酸序列与SpeF（促有丝分裂因子）相同。此外，用纯化的SpeF免疫制备的抗SpeF抗血清消除了纯化条带的血管通透性活性。用从已发表的SpeF序列衍生的合成肽免疫制备的抗血清也中和了这种活性。这些结果表明，链球菌SpeF是肺血管通透性增加的主要原因，并且在化脓性链球菌引起的TSLS条件下足以导致ARDS的发病机制。
