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Cytosolic Phospholipase A2α Promotes Pulmonary Inflammation and Systemic Disease during Streptococcus pneumoniae

Rudra Bhowmick1, Stacie Clark2, Joseph V Bonventre3

  • 1School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, USA.

Infection and Immunity
|August 16, 2017
PubMed

Insights

Group IVA cytosolic phospholipase A2 (cPLA2α) drives pulmonary inflammation and lethal systemic infection in Streptococcus pneumoniae pneumonia. Inhibiting cPLA2α significantly reduces inflammation and improves survival, highlighting its role in bacterial spread.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pathology

Background:

  • Streptococcus pneumoniae causes pulmonary infections with neutrophil infiltration.
  • 12-lipoxygenase (12-LOX) promotes inflammation and systemic spread by generating hepoxilin A3 (HXA3).
  • Phospholipase A2 (PLA2) releases arachidonic acid (AA), a precursor for HXA3.

Purpose of the Study:

  • To investigate the role of PLA2 in local and systemic disease during S. pneumoniae infection.
  • To determine the specific involvement of group IVA cytosolic PLA2 (cPLA2α) in pneumococcal pneumonia.

Main Methods:

  • Studied cPLA2α activation in lung epithelial cells infected with S. pneumoniae.
  • Assessed the impact of cPLA2α inhibition on neutrophil migration in vitro.
  • Utilized cPLA2α-deficient mice for pulmonary challenge experiments with S. pneumoniae.

Main Results:

  • cPLA2α activation was observed in infected lung epithelial cells, critical for AA release.
  • Pharmacological inhibition of cPLA2α blocked S. pneumoniae-induced neutrophil migration.
  • cPLA2α-deficient mice showed reduced lung inflammation, no bacteremia, and improved survival against lethal S. pneumoniae challenge.

Conclusions:

  • cPLA2α is crucial for initiating pulmonary inflammation in pneumococcal infections.
  • cPLA2α activity is required for lethal systemic infection following S. pneumoniae lung challenge.
  • Targeting cPLA2α may offer a therapeutic strategy against severe pneumococcal pneumonia.
Keywords:
Streptococcus pneumoniaeinflammationneutrophilsphospholipase

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