TY - JOUR
T1 - Role of lung surfactant in phagocytic clearance of apoptotic cells by macrophages in rats
AU - Wang, Liying
AU - Scabilloni, James F.
AU - Antonini, James M.
AU - Castranova, Vincent
AU - Rojanasakul, Yon
AU - Roberts, Jenny R.
AU - Zhang, Zhuo
AU - Mercer, Robert R.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/5
Y1 - 2006/5
N2 - Two of the common features of inflammatory lung diseases are the increased production of pulmonary surfactant and the induction of lung cell apoptosis. However, the relationship between these two events has not been addressed. To investigate the role of surfactant in pulmonary inflammation and apoptosis, we instilled natural lung surfactant (Survanta) (1.6-12.5 mg) into the rat lungs and determined the number of alveolar macrophages (AMs) and apoptotic lung cells. High-dose treatments of Survanta (>6.25 mg/rat) caused an increase in macrophage cell influx and lung cell apoptosis at 4 weeks post-treatment. In vitro studies using lavaged macrophages showed Survanta did not cause apoptosis. We then examined the role of Survanta on ability of macrophages phagocytizing apoptotic cells. This study demonstrated that macrophages were able to eliminate apoptotic cells more efficiently in the absence of surfactant than in its presence. In vivo, high doses of Survanta decreased the ability to clear exogenously instilled apoptotic cells or bacteria. Taken together, our results suggest that excessive accumulation of lung surfactant by Survanta treatment can impair or overwhelm the phagocytic clearance function of AMs and that this impairment may lead to increased presence of apoptotic cells in the lung and bacterial survival.
AB - Two of the common features of inflammatory lung diseases are the increased production of pulmonary surfactant and the induction of lung cell apoptosis. However, the relationship between these two events has not been addressed. To investigate the role of surfactant in pulmonary inflammation and apoptosis, we instilled natural lung surfactant (Survanta) (1.6-12.5 mg) into the rat lungs and determined the number of alveolar macrophages (AMs) and apoptotic lung cells. High-dose treatments of Survanta (>6.25 mg/rat) caused an increase in macrophage cell influx and lung cell apoptosis at 4 weeks post-treatment. In vitro studies using lavaged macrophages showed Survanta did not cause apoptosis. We then examined the role of Survanta on ability of macrophages phagocytizing apoptotic cells. This study demonstrated that macrophages were able to eliminate apoptotic cells more efficiently in the absence of surfactant than in its presence. In vivo, high doses of Survanta decreased the ability to clear exogenously instilled apoptotic cells or bacteria. Taken together, our results suggest that excessive accumulation of lung surfactant by Survanta treatment can impair or overwhelm the phagocytic clearance function of AMs and that this impairment may lead to increased presence of apoptotic cells in the lung and bacterial survival.
KW - Alveolar macrophage
KW - Apoptosis
KW - Clearance
KW - Rat lung
KW - Survanta
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U2 - 10.1038/labinvest.3700406
DO - 10.1038/labinvest.3700406
M3 - Article
C2 - 16534500
AN - SCOPUS:33646133663
SN - 0023-6837
VL - 86
SP - 458
EP - 466
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 5
ER -