STREPTOCOCCAL CYSTEINE PROTEASE AUGMENTS LUNG INJURY-INDUCED BY PRODUCTS OF GROUP-A STREPTOCOCCI

Streptacoccus pyogenes infections in humans may be associated with sev ere clinical manifestations, including adult respiratory distress synd rome and a toxic shock-like syndrome. These observations have led to t he investigation of products of group A streptococci that may contribu te to Increased virulence. Streptococcal pyrogenic exotoxin B is a hig hly conserved precursor of an extracellular cysteine protease that is secreted hy S. pyogenes. We investigated the ability of this streptoco ccal cysteine protease (SCP) to act synergistically with either strept ococcal cell wall antigen (SCW) or streptolysin-O (SLO) to augment lun g injury in rats. Intratracheal administration of either SCW or SLO al one caused lung injury, as measured by pulmonary vascular leak, Bronch oalveolar lavage (BAL) fluid analysis showed that SCW induced neutroph il accumulation and appearance of interleukin-1 beta and tumor necrosi s factor alpha. In contrast, SLO induced neither neutrophil influx nor significant cytokine elevations in BAL fluids. Intratracheal administ ration of SCP with either SCW or SLO resulted in synergistic augmentat ion of lung vascular permeability and accumulation of BAL neutrophils, The synergy was reduced when SCP was either heat inactivated or coins tilled with a peptide Inhibitor of the protease. SCP in the presence o f SCW resulted in a significant increase in BAL fluid tumor necrosis f actor alpha content but not in immunoreactive interleukin-1 beta. More over, the copresence of SCP with SCW resulted in increased Bit fluid n itrite-nitrate levels, indicative of nitric oxide production, These da ta demonstrate that SCP acts synergistically with other S. pyogenes pr oducts (SCW or SLO) to increase tissue injury and provide additional e vidence that SCP may function as an important virulence factor in grou p A streptococcal infections.