Recombinant chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) protects against LPS-induced lung injury in mice

Clin Immunol. 2018 Dec:197:27-33. doi: 10.1016/j.clim.2018.08.009. Epub 2018 Aug 23.

Abstract

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are clinical conditions caused by trauma, lung infection or sepsis. ALI/ARDS is associated with massive recruitment of neutrophils into the lung with release of reactive oxygen species and excessive inflammatory response that damage alveolar tissue. Here we report the successful use of a potent recombinant chemotaxis inhibitory protein (rCHIPS) derived from Staphylococcus aureus in reducing the severity of ALI/ARDS. Treatment with rCHIPS reduces pulmonary inflammation and permeability in mice after intranasal administration of lipopolysaccharide (LPS). rCHIPS treatment significantly reduces lung myeloperoxidase (MPO) activity, pro-inflammatory cytokines, broncho-alveolar lavage (BAL) fluid protein content as well as histopathological changes. In addition, treatment with rCHIPS significantly diminishes neutrophils and leukocytes recruitment into lung tissue after LPS administration and hence protects mice from reactive oxygen species mediated lung injury. Our finding reveals potential therapeutic benefits of using rCHIPS for the treatment of ALI/ARDS.

Keywords: ALI; ARDS; CHIPS; LPS; PMN.

MeSH terms

  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / pathology
  • Animals
  • Bacterial Proteins / pharmacology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cytokines / drug effects*
  • Cytokines / metabolism
  • Female
  • Lipopolysaccharides / pharmacology*
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects*
  • Permeability / drug effects
  • Peroxidase / drug effects*
  • Peroxidase / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Bacterial Proteins
  • Cytokines
  • Lipopolysaccharides
  • Recombinant Proteins
  • chemotaxis inhibitory protein, Staphylococcus aureus
  • Peroxidase