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Eliana Garcia-Vaz

Eliana Garcia Vaz

Postdoctoral fellow

Eliana Garcia-Vaz

Streptococcal M1 protein triggers chemokine formation, neutrophil infiltration, and lung injury in an NFAT-dependent manner.

Author

  • Songen Zhang
  • Su Zhang
  • Eliana Garcia Vaz
  • Heiko Herwald
  • Maria Gomez
  • Henrik Thorlacius

Summary, in English

Streptococcus pyogenes of the M1 serotype can cause STSS, which is associated with significant morbidity and mortality. The purpose of the present study was to examine the role of NFAT signaling in M1 protein-induced lung injury. NFAT-luc mice were treated with the NFAT inhibitor A-285222 before administration of the M1 protein. Neutrophil infiltration, edema, and CXC chemokines were quantified in the lung, 4 h after challenge with the M1 protein. Flow cytometry was used to determine Mac-1 expression. Challenge with the M1 protein increased NFAT-dependent transcriptional activity in the lung, spleen, and liver in NFAT-luc mice. Administration of the NFAT inhibitor A-285222 abolished M1 protein-evoked NFAT activation in the lung, spleen, and liver. M1 protein challenge induced neutrophil recruitment, edema, and CXC chemokine production in the lung, as well as up-regulation of Mac-1 on circulating neutrophils. Inhibition of NFAT activity attenuated M1 protein-induced neutrophil infiltration by 77% and edema formation by 50% in the lung. Moreover, administration of A-285222 reduced M1 protein-evoked pulmonary formation of CXC chemokine >80%. In addition, NFAT inhibition decreased M1 protein-triggered Mac-1 up-regulation on neutrophils. These findings indicate that NFAT signaling controls pulmonary infiltration of neutrophils in response to streptococcal M1 protein via formation of CXC chemokines and neutrophil expression of Mac-1. Thus, the targeting of NFAT activity might be a useful way to ameliorate lung injury in streptococcal infections.

Department/s

  • Surgery
  • Diabetic Complications
  • Infection Medicine (BMC)
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2015

Language

English

Pages

1003-1010

Publication/Series

Journal of Leukocyte Biology

Volume

97

Issue

6

Document type

Journal article

Publisher

John Wiley and Sons

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Surgery
  • Diabetic Complications

ISBN/ISSN/Other

  • ISSN: 1938-3673