Surfactant therapy of newborn rabbits impairs lung macrophage bactericidal activity

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Abstract
Because in vitro studies indicate that pulmonary alveolar macrophages (PAM''s) filled with phospholipid vesicles have depressed microbicidal capacity, we tested the intrapulmonary bactericidal activity of newborn PAM''s after surfactant treatment. Term newborn rabbits received intratracheally either homologous surfactant or one of two artificial phospholipid vesicle preparations followed by pulmonary aerosol infection with group B streptococci (GBS). Four hours after lung infection, phagocytic killing of GBS was reduced by 70-90% in animals treated with the homologous and one of the artificial surfactants compared with untreated animals or animals that received intrapulmonary injections of the surfactant vehicle (P < 0.02). The other artificial phospholipid preparation decreased intrapulmonary inactivation of GBS by 30-40% compared with the controls. The phospholipid vesicles in the three preparations were avidly ingested and processed by newborn PAM''s. The diminished in vivo killing of GBS was not attributed to decreased viability or phagocytic behavior of the PAM''s toward GBS. The bactericidal defect that was evident in the newborn PAM''s appeared related to the uptake of large phospholipid vesicles in the preparations rather than to the phospholipid content of the surfactants themselves. When in vitro conditions that stimulated the alveolar environment were used, the natural surfactant preparation promoted GBS proliferation, whereas the artificial preparations did not. Our findings indicate that surfactant administration reduces the bactericidal activity of neonatal PAM''s. We conclude that additional investigations are needed to ascertain the effect of surfactant replacement therapy on host defenses of the lung.