The role of alveolar macrophages in the pathogenesis of aspiration pneumonitis

Rationale: A robust TNFα 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 TNFα release by the alveolar and peritoneal macrophages following in vivo and in vitro exposure to acid and/or food particles. TNFα release by macrophages was examined in response to E. coli lipopolysaccaride (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 TNFα 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.