Meconium inhibits phagocytosis and stimulates respiratory burst in alveolar macrophages.
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. Short-term exposure of rat NR8383 AMs to sterile meconium from human or equine neonates (1.2-24 mg/mL) produced a dose-dependent 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) showed DNA fragmentation indicative of apoptosis. Meconium therefore may interfere with AM function by inducing oxidative stress and apoptosis. Tissue injury from release of reactive oxygen species by AMs may be important in the pathophysiology of the meconium aspiration syndrome.
Craig
Sylvia
S
Department of Pathology, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada. sylvia.craig@dal.ca
Lopez
Alfonso
A
Hoskin
David
D
Markham
Fred
F
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006736:Horses; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D016676:Macrophages, Alveolar / Q000473:pathology / Q000502:physiology*; D008470:Meconium / Q000502:physiology*; D008471:Meconium Aspiration Syndrome / Q000473:pathology / Q000503:physiopathology; D010587:Phagocytosis; D051381:Rats; D016897:Respiratory Burst
D000242:Cyclic AMP