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Respiratory Research 2012
Poractant alfa (Curosurf?) increases phagocytosis of apoptotic neutrophils by alveolar macrophages in vivoKeywords: Inflammation, Resolution, Anti inflammation, Drug therapy, Surfactant Abstract: Poractant alfa (200 mg/kg) was instilled intratracheally in the lungs of three months old adult male C57/Black 6 mice, followed by apoptotic neutrophil instillation. Bronchoalveloar lavage was performed and alveolar macrophages and neutrophils were counted. Phagocytosis of apoptotic neutrophils was quantified by determining the number of apoptotic neutrophils per alveolar macrophages.Exogenous surfactant increased the number of alveolar macrophages engulfing apoptotic neutrophils 2.6 fold. The phagocytosis of apoptotic neutrophils was increased in the presence of exogenous surfactant by a 4.7 fold increase in phagocytosed apoptotic neutrophils per alveolar macrophage.We conclude that the anti-inflammatory properties of surfactant therapy may be mediated in part by increased numbers of alveolar macrophages and increased phagocytosis of apoptotic neutrophils by alveolar macrophages.Apoptosis and apoptotic cell clearance are recognized as important mechanisms in resolving inflammation, maintaining homeostasis and tissue remodeling, e.g. during ontogeny and repair [1]. Inefficient apoptotic cell clearance results in necrosis or cytolysis, which leads to the release of noxious cellular contents into surrounding tissues and consequently tissue damage and prolonged inflammation [1].Efficient clearance of these apoptotic cells by phagocytes critically depends on a sequence of events. Firstly, the apoptotic cells undergo changes which target them for clearance, e.g. the loss of phospholipid asymmetry exposes phosphatidylserine on their cell surface [2]. Secondly, these changes of the cell surface need to be recognized by the phagocytes followed by their engulfment. This can be achieved through phagocyte receptors that interact directly with apoptotic cells and receptors that interact through intermediate soluble bridging molecules, like C1q and mannose-binding lectin, which attach to the surface of the apoptotic cells [3,4].The efficient clearance of apoptotic cells and the
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