Streptococcal cysteine protease augments lung injury induced by products of group A streptococci

Thomas P. Shanley, Dennis Schrier, Vivek Kapur, Michael Kehoe, James M. Musser, Peter A. Ward

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Streptococcus pyogenes infections in humans may be associated with severe clinical manifestations, including adult respiratory distress syndrome and a toxic shock-like syndrome. These observations have led to the investigation of products of group A streptococci that may contribute to increased virulence. Streptococcal pyrogenic exotoxin B is a highly conserved precursor of an extracellular cysteine protease that is secreted by S. pyogenes. We investigated the ability of this streptococcal cysteine protease (SCP) to act synergistically with either streptococcal cell wall antigen (SCW) or streptolysin-O (SLO) to augment lung injury in rats. Intratracheal administration of either SCW or SLO alone caused lung injury, as measured by pulmonary vascular leak. Bronchoalveolar lavage (BAL) fluid analysis showed that SCW induced neutrophil accumulation and appearance of interleukin-1β and tumor necrosis factor alpha. In contrast, SLO induced neither neutrophil influx nor significant cytokine elevations in BAL fluids. Intratracheal administration of SCP with either SCW or SLO resulted in synergistic augmentation of lung vascular permeability and accumulation of BAL neutrophils. The synergy was reduced when SCP was either heat inactivated or coinstilled with a peptide inhibitor of the protease. SCP in the presence of SCW resulted in a significant increase in BAL fluid tumor necrosis factor alpha content but not in immunoreactive interleukin-1β. Moreover, the copresence of SCP with SCW resulted in increased BAL fluid nitrite-nitrate levels, indicative of nitric oxide production. These data demonstrate that SCP acts synergistically with other S. pyogenes products (SCW or SLO) to increase tissue injury and provide additional evidence that SCP may function as an important virulence factor in group A streptococcal infections.

Original languageEnglish (US)
Pages (from-to)870-877
Number of pages8
JournalInfection and Immunity
Volume64
Issue number3
StatePublished - Mar 4 1996

Fingerprint

Cysteine Proteases
Lung Injury
Streptococcus
Cell Wall
Antigens
Bronchoalveolar Lavage Fluid
Streptococcus pyogenes
Neutrophils
Interleukin-1
Tumor Necrosis Factor-alpha
Streptococcal Infections
Lung
Adult Respiratory Distress Syndrome
Capillary Permeability
Bronchoalveolar Lavage
Virulence Factors
Septic Shock
Nitrites
Protease Inhibitors
Nitrates

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Shanley, T. P., Schrier, D., Kapur, V., Kehoe, M., Musser, J. M., & Ward, P. A. (1996). Streptococcal cysteine protease augments lung injury induced by products of group A streptococci. Infection and Immunity, 64(3), 870-877.
Shanley, Thomas P. ; Schrier, Dennis ; Kapur, Vivek ; Kehoe, Michael ; Musser, James M. ; Ward, Peter A. / Streptococcal cysteine protease augments lung injury induced by products of group A streptococci. In: Infection and Immunity. 1996 ; Vol. 64, No. 3. pp. 870-877.
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Shanley, TP, Schrier, D, Kapur, V, Kehoe, M, Musser, JM & Ward, PA 1996, 'Streptococcal cysteine protease augments lung injury induced by products of group A streptococci', Infection and Immunity, vol. 64, no. 3, pp. 870-877.

Streptococcal cysteine protease augments lung injury induced by products of group A streptococci. / Shanley, Thomas P.; Schrier, Dennis; Kapur, Vivek; Kehoe, Michael; Musser, James M.; Ward, Peter A.

In: Infection and Immunity, Vol. 64, No. 3, 04.03.1996, p. 870-877.

Research output: Contribution to journalArticle

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T1 - Streptococcal cysteine protease augments lung injury induced by products of group A streptococci

AU - Shanley, Thomas P.

AU - Schrier, Dennis

AU - Kapur, Vivek

AU - Kehoe, Michael

AU - Musser, James M.

AU - Ward, Peter A.

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N2 - Streptococcus pyogenes infections in humans may be associated with severe clinical manifestations, including adult respiratory distress syndrome and a toxic shock-like syndrome. These observations have led to the investigation of products of group A streptococci that may contribute to increased virulence. Streptococcal pyrogenic exotoxin B is a highly conserved precursor of an extracellular cysteine protease that is secreted by S. pyogenes. We investigated the ability of this streptococcal cysteine protease (SCP) to act synergistically with either streptococcal cell wall antigen (SCW) or streptolysin-O (SLO) to augment lung injury in rats. Intratracheal administration of either SCW or SLO alone caused lung injury, as measured by pulmonary vascular leak. Bronchoalveolar lavage (BAL) fluid analysis showed that SCW induced neutrophil accumulation and appearance of interleukin-1β and tumor necrosis factor alpha. In contrast, SLO induced neither neutrophil influx nor significant cytokine elevations in BAL fluids. Intratracheal administration of SCP with either SCW or SLO resulted in synergistic augmentation of lung vascular permeability and accumulation of BAL neutrophils. The synergy was reduced when SCP was either heat inactivated or coinstilled with a peptide inhibitor of the protease. SCP in the presence of SCW resulted in a significant increase in BAL fluid tumor necrosis factor alpha content but not in immunoreactive interleukin-1β. Moreover, the copresence of SCP with SCW resulted in increased BAL fluid nitrite-nitrate levels, indicative of nitric oxide production. These data demonstrate that SCP acts synergistically with other S. pyogenes products (SCW or SLO) to increase tissue injury and provide additional evidence that SCP may function as an important virulence factor in group A streptococcal infections.

AB - Streptococcus pyogenes infections in humans may be associated with severe clinical manifestations, including adult respiratory distress syndrome and a toxic shock-like syndrome. These observations have led to the investigation of products of group A streptococci that may contribute to increased virulence. Streptococcal pyrogenic exotoxin B is a highly conserved precursor of an extracellular cysteine protease that is secreted by S. pyogenes. We investigated the ability of this streptococcal cysteine protease (SCP) to act synergistically with either streptococcal cell wall antigen (SCW) or streptolysin-O (SLO) to augment lung injury in rats. Intratracheal administration of either SCW or SLO alone caused lung injury, as measured by pulmonary vascular leak. Bronchoalveolar lavage (BAL) fluid analysis showed that SCW induced neutrophil accumulation and appearance of interleukin-1β and tumor necrosis factor alpha. In contrast, SLO induced neither neutrophil influx nor significant cytokine elevations in BAL fluids. Intratracheal administration of SCP with either SCW or SLO resulted in synergistic augmentation of lung vascular permeability and accumulation of BAL neutrophils. The synergy was reduced when SCP was either heat inactivated or coinstilled with a peptide inhibitor of the protease. SCP in the presence of SCW resulted in a significant increase in BAL fluid tumor necrosis factor alpha content but not in immunoreactive interleukin-1β. Moreover, the copresence of SCP with SCW resulted in increased BAL fluid nitrite-nitrate levels, indicative of nitric oxide production. These data demonstrate that SCP acts synergistically with other S. pyogenes products (SCW or SLO) to increase tissue injury and provide additional evidence that SCP may function as an important virulence factor in group A streptococcal infections.

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