Abstract
BackgroundAlveolar 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.MethodsLipopolysaccharide 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.ResultsA 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.ConclusionThese data suggest that alveolar macorphages 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.
Highlights
Lipopolysaccharide (LPS) is a component of the outer membrane of gram-negative bacteria, capable of inducing severe lung injury in sepsis or bacterial pneumonia upon release
During the development of an acute inflammatory lung injury, alveolar macrophages (AM) play a very important role upon their activation. It has been shown in several lung injury models that activated pulmonary macrophages release the cytokines tumor necrosis factorα (TNF-α) and interleukin-1β (IL-1β) as well as the chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) [5]
Adhesion to vascular endothelium mediated through ICAM-1/VCAM-1-integrin interactions is a key step in emigration of white blood cells to sites of inflammation [6]
Summary
Lipopolysaccharide (LPS) is a component of the outer membrane of gram-negative bacteria, capable of inducing severe lung injury in sepsis or bacterial pneumonia upon release. Both conditions are predisposing causes of the acute respiratory distress syndrome (ARDS). Only sparse data exist about the exact role of effector cells such as alveolar macrophages (AM) in the respiratory compartment in this type of injury. Alveolar macrophages play an important role during the development of acute inflammatory lung injury. 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
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