The role of alveolar macrophages in the pathogenesis of aspiration pneumonitis

Immunol Invest. 2007;36(4):457-71. doi: 10.1080/08820130701361053.

Abstract

Rationale: A robust TNFalpha response is seen following aspiration of food particles, while there is only a modest response to acid.

Objectives: To examine the direct effects of acid and particulate components of gastric content on local and systemic macrophages.

Methods: Pathogen-free Long-Evans rats were injured with intratracheal instillation of normal saline (SHAM), low pH saline (ACID), small non-acidic particles (SNAP) or acidified particles (CASP). The alveolar (local) and the peritoneal (systemic) macrophages were harvested following the injury.

Measurements: We examined the phagocytic activity and TNFalpha release by the alveolar and peritoneal macrophages following in vivo and in vitro exposure to acid and/or food particles. TNFalpha release by macrophages was examined in response to E. coli lipopolysaccharide (LPS) stimulation.

Main results: In rats injured with gastric particles, the number of the mononuclear cells was higher than those obtained from acid-injured animals. Both in vivo and in vitro exposure of the alveolar macrophages to SNAP resulted in increased production of TNFalpha within 8 hours. Transient exposure of the alveolar macrophages to a low pH environment suppressed LPS-induced production of this cytokine. Additionally, the phagocytic activity of the alveolar macrophages was inhibited by in vitro exposure of the macrophages to acid.

Conclusions: We conclude that the two components of gastric aspiration have diverse effects on local and systemic macrophages. Although there is a synergy between acid and gastric particulate in producing an acute lung injury, the modulatory effects of these injuries on the alveolar macrophages are averse.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Hydrogen-Ion Concentration
  • Lipopolysaccharides / immunology
  • Macrophage Activation*
  • Macrophages, Alveolar / immunology*
  • Macrophages, Peritoneal / immunology
  • Male
  • Phagocytosis
  • Pneumonia, Aspiration / immunology*
  • Pneumonia, Aspiration / physiopathology
  • Rats
  • Rats, Long-Evans
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha