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The meconium aspiration syndrome is an important cause of respiratory distress in newborn infants. Alveolar macrophages (AMs) provide a first line of defense in the lower respiratory tract against inhaled pathogens and particles such as meconium. In this study, we examined the effect of meconium on two primary macrophage functions: phagocytosis and respiratory burst. Shortterm exposure of rat NR8383 AMs to sterile meconium from human or equine neonates (1.2-24 mg/mL) produced a dosedependent decrease in phagocytosis of fluorescent latex beads. This effect was not due to decreased cell viability or to an elevation of intracellular cAMP. The effect of short-term exposure to meconium on the respiratory burst response in AMs was quantified using flow cytometry to measure oxidation of dichlorofluorescin diacetate. A robust respiratory burst was triggered when AMs were exposed to 12 or 24 mg/mL meconium. This effect was attenuated but not eliminated by filtration of the meconium. However, subsequent to meconium exposure, AMs had a reduced respiratory burst in response to stimulation with phorbol myristate acetate. In addition, AMs that were exposed to meconium for an extended period (24 h Meconium aspiration syndrome (MAS) is an important cause of respiratory distress in newborn infants (1). Approximately 12-15% of human infants are born through meconiumcontaminated amniotic fluid (2), and these infants are much more likely to develop respiratory distress and require respiratory support (3). When meconium is present in the amniotic fluid,~5% of neonates will develop MAS, and~5% or more of these infants will die (2).The pathophysiology of MAS is complex and involves airway obstruction, surfactant dysfunction, and pulmonary inflammation (4). Alveolar macrophages (AMs) are important in defending the alveolar space against inhaled pathogens and particles. Because the phagocytic activity of AMs is a crucial component of host defense, it is important to know the effect of meconium on phagocytosis. Meconium has been shown to decrease phagocytosis by neutrophils in vitro (5), so it is reasonable to postulate that AM phagocytic activity may also be adversely affected.Once phagocytosis has occurred, macrophages undergo an oxidative metabolic process called respiratory burst, generating reactive oxygen species (ROS) with activity against a wide range of invading organisms. Although production of antimicrobial molecules is essential in host defense, excessive ROS production can also cause injury to surrounding tissue (6,7). For example, ROS generated through respiratory burst activity plays a role in inducing pulmonary injury in diseases such as acute respiratory distress syndrome (8) and may also contribute to the pathophysiology of MAS. The purpose of this study was to investigate the effect of meconium on the phagocytic activity and respiratory burst response of AMs. METHODS Cells.A continuous rat AM cell line, NR8383 (9)

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