Metabolism of Exogenously Administered Natural Surfactant in the Newborn Lamb

Abstract

Summawre~orted t1 12 may be in error due to continued secretion of isoto~e[3H]-Palmitate labeled natural lamb surfactant and free [14C]-choline were mixed with the lung fluid of 11 term lambs at cesarean section, before the first breath. After receiving the isotope, the lambs were delivered, allowed to breathe spontaneously, and were subsequently sacrificed from 5 min to % h of age. Alveolar washes, lung homogenates, microsomal and lamellar body fractions of lungs, and pulmonary alveolar macrophages were examined for the presence of labeled phosphatidylcholine. Analysis of the labeled natural surfactant kinetic data revealed an apparent tlIz of phosphatidvlcholine in the whole lung of 6.0 davs. This half-life can be interpreted only as a rough estimate." Appearance of considerable I3H] labeled phosphatidylcholine in the lung homogenates demonstrated uptake of phosphatidylcholine from alveoli into lung tissue. The surfactant-associated label in homogenates was localized preferentially to lamellar body fractions. Some of the administered ['4CI-choline appeared in phosphatidylcholine. Almost all of this labeled phosphatidylcholine was associated with the homogenate. Extremely small % of administered I3HI and Ir4C] were found in pulmonary alveolar macrophages. SpeculationThe prolonged tl/z measured in this study indicates very slow turnover of alveolar phosphatidylcholine and/or considerable reutilization of label and possibly of the entire phosphatidylcholine molecule. The concentration of label in lamellar bodies raises the possibility that alveolar phosphatidylcholine may be degraded and its components utilized for synthesis of new phosphatidylcholine or that alveolar phosphatidylcholine may be absorbed into type-2 alveolar cells and resecreted intact. The finding of [l4Cl labeled phosphatidylcholine in lung homogenate but not in alveolar wash indicates that, even if choline were released by intra-alveolar degradation of surfactant, it is not used to a significant degree for synthesis of new surfactant phosphatidylcholine.The ultimate fate of surfactant phospholipids, once secreted into the alveoli, remains to be defined. Reasonable speculations include: (1) removal via the lymphatic or circulatory systems, (2) metabolism by alveolar macrophages, (3) surface spreading into the airways, or (4) reuptake into pulmonary parenchymal cells with reutilization of all or part of the phospholipid molecule. Estimates of the biologic half-life (tl/z) of surfactant phospholipids in lung parenchyma and in the alveoli have been derived by utilizing radiolabeled phospholipid precursors. The estimated half-life values vary, depending on type of labeled phospholipid precursor used, type of animal studied, and the maturity of the animals. An approximate tlI2 of 16 h has been reported for lung phosphatidylcholine (PC) in adult rats and rabbits, using radiolabeled palmitic acid as a precursor (10,11,19,20). Again using labeled palmitic acid, the biologic ttI2 for alveolar surfactant was estimated to be 54 and 45 h in newborn and adul...

Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies

“…The slow secretion and reduced alveolar accumulation of surfactant are balanced in term and preterm lungs by a rather slow catabolism. For example, the half-life of radiolabeled surfactant phospholipids given endotracheally to term lambs is about 6 days [26]. However, in preterm baboons using the same method, the half-life is about 30 h [27], which may be due to more recycling in preterm animals and to species difference.…”

Surfactant Metabolism in the Neonate

“…For example, the half-life of radiolabeled surfactant phospholipid given endotracheally to term lambs is about 6 days [26] . However, in premature baboons using the same method the half-life is about 30 h [27] , which may be due to more recycling in premature animals, and to species difference.…”

Plasma concentration of elastase-alpha 1-proteinase inhibitor complex in surfactant-treated preterm neonates with respiratory distress syndrome

“…A possible mechanism may be phagocytosis-mediated activation of pulmonary macrophages, which were shown to ingest surfactant components, such as phospholipids and xenogenic proteins [2]. Subsequent phagocytosis-associated cytokine release may be followed by PMN activation and extracellular release of elastase.…”

“…However, immunological side-effects induced by surfactant constituents have received little attention. Phagocytosis of surfactant by pulmonary macrophages [2,3], antibody formation against surfactant components [4], enhancement of pulmonary leucostasis following surfactant replacement [5], and contamination of natural surfactant preparations with platelet-activating factor (PAF) [6] have been observed, and raise the question of the induction of an inflammatory response by such treatment.…”