Alveolar macrophages regulate neutrophil recruitment in endotoxin-induced lung injury.
BACKGROUND
Alveolar macrophages play an important role during the development of acute inflammatory lung injury. In the present study, in vivo alveolar macrophage depletion was performed by intratracheal application of dichloromethylene diphosphonate-liposomes in order to study the role of these effector cells in the early endotoxin-induced lung injury.


METHODS
Lipopolysaccharide was applied intratracheally and the inflammatory reaction was assessed 4 hours later. Neutrophil accumulation and expression of inflammatory mediators were determined. To further analyze in vivo observations, in vitro experiments with alveolar epithelial cells and alveolar macrophages were performed.


RESULTS
A 320% increase of polymorphonuclear leukocytes in bronchoalveolar lavage fluid was observed in macrophage-depleted compared to macrophage-competent lipopolysaccharide-animals. This neutrophil recruitment was also confirmed in the interstitial space. Monocyte chemoattractant protein-1 concentration in bronchoalveolar lavage fluid was significantly increased in the absence of alveolar macrophages. This phenomenon was underlined by in vitro experiments with alveolar epithelial cells and alveolar macrophages. Neutralizing monocyte chemoattractant protein-1 in the airways diminished neutrophil accumulation.


CONCLUSIONS
These data suggest that alveolar macrophages play an important role in early endotoxin-induced lung injury. They prevent neutrophil influx by controlling monocyte chemoattractant protein-1 production through alveolar epithelial cells. Alveolar macrophages might therefore possess robust anti-inflammatory effects.
Institute of Anesthesiology, University of Zurich, Switzerland. Beatrice_Beck.Schimmer@access.unizh.ch
Beatrice
B
Beck-Schimmer
Reto
R
Schwendener
Thomas
T
Pasch
Livia
L
Reyes
Christa
C
Booy
Ralph C
RC
Schimmer
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology*; D004731:Endotoxins; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D018932:Chemokine CCL2; D004731:Endotoxins; D008070:Lipopolysaccharides