文本框: Concepts of Surfactant Biology and Pharmacology Relevant to Neonatal Lung Function Bengt Robertson, Laboratory for Surfactant Research, Department of Surgical Sciences, Karolinska Hospital, L73, SE-171 76 Stockholm, Sweden Lung surfactant is of crucial importance in the neonatal period. Large amounts of surfactant accumulate in the fetal lung near term to become secreted into the alveolar spaces under the influence of a surge of circulating catecholamines during the ‘stress of birth’. It has been estimated that the mature lung has a pool size of alveolar surfactant of about 100 mg/kg body weight. This figure, which is of the same order as the dose of exogenous surfactant usually recommended for treatment of babies with respiratory distress syndrome, is about ten times larger than the corresponding figure for the normal adult lung, and more than 25 times larger than the amount of surfactant lipids required to coat the inside of the lung with a monolayer. We probably need so much surfactant at birth because the fetal alveolar compartment is filled with liquid before the onset of breathing. Kobayashi et al (Respir Physiol 80:181-192, 1990) estimated the ‘critical concentration’ of surfactant (i.e., the minimum concentration required to ensure effective air expansion of the lung at birth) to about 3.5 mg/ml, a figure quite similar to the pool size estimates given above (assuming uniform distribution of the surfactant material) divided by the volume of the liquid-filled fetal lung (about 30 ml/kg body weight). The four surfactant proteins (SP-A, B, C, D) have been studied intensively in recent years and their functional significance has been examined in gene-targeted ’knockout’ mice, and by experimental blocking of the individual proteins with monoclonal antibodies. Although SP-A is required (together with SP-B and surfactant lipids) for transformation of lamellar bodies to tubular myelin, SP-A knockout-mice have no respiratory problems at birth; however, these -/- mice have increased susceptibility to infection with various microorganisms including group B streptococci. In contrast, SP-B knockout-mice develop severe respiratory failure soon after birth, associated with accumulation of pro-SP-C in the airspaces, indicating that the metabolic pathways for these two surfactant proteins are intertwined. SP-C is the most abundant hydrophobic surfactant protein on a molar basis and its amino acid sequence is largely conserved during evolution, suggesting that this protein has some important physiological function. Surprisingly, SP-C knockout mice have essentially normal phenotype and do not develop respiratory failure at birth. On the other hand, neonatal inflammatory lung disease associated with absence or very low levels of SP-C has been described in Belgian White and Blue calves (sick animals had normal levels of SP-B) and the first cases of apparently familial chronic fibrosing lung disease were recently reported by Nogee et al (N Engl J Med 344:573-579, 2001). SP-D knockout-mice have normal lung function at birth but gradually accumulate surfactant lipids in peripheral airspaces, with histological features reminiscent of alveolar lipoproteinosis. These new observations support that SP-D has a role in the clearence of surfactant from the airspaces. Inactivation of surfactant by aspirated material or plasma proteins……