The role of alveolar macrophages in the pathogenesis of aspiration pneumonitis.
BACKGROUND
A robust TNFalpha response is seen following aspiration of food particles, while there is only a modest response to acid.


OBJECTIVE
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.


METHODS
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.


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.
Nader
Nader D
ND
Department of Anesthesiology, University at Buffalo, State University of New York, Buffalo, New York 14215, USA. nnader@buffalo.edu
McQuiller
Peter S
PS
Raghavendran
Krishnan
K
Spengler
R N
RN
Knight
Paul R
PR
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D010587:Phagocytosis; D011015:Pneumonia, Aspiration / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha