We have used radiolabeled natural surfactants, phospholipid analogues, and liposomes of dipalmitoylphosphatidylcholine to probe surfactant metabolism in developing and adult rabbits. We find overall clearance from the lungs of labeled phospholipids to be much more rapid in adult than developing rabbits, in part because reutilization of surfactant is much more efficient in the developing rabbit. We also find differences in clearance of radiolabeled phospholipids from lungs that relate to natural surfactant dose, species source of a natural surfactant, and phospholipid aggregate form (liposomes). While a number of investigators have commented on possible catabolic pathways for surfactant, suractant clearance and catabolism have not been considered within the context of presently developing concepts of surfactant kinetics, function and reutilization. This grant proposes a series of experiments to evaluate in an integrated manner surfactant catabolism and clearance from the lungs of rabbits. The specific probes of surfactant catabolic pathways will be natural rabbit surfactant with multiply labeled phosphatidylcholine, liposomes of 3 types, labeled surfactant from another species, radiolabeled analogues of phosphatidylcholine, and dosage of the surfactant. Catabolic pathways will be defined by tracing labeled total and saturated phosphatidylcholines through lung fractions and body fractions. A major goal will be to define the differences in catabolic pathways that must exist between developing and mature rabbits. These experiments will define how lung catabolic and clearance pathways differ for different surfactants. The results will have direct relevance for the fate of exogenously administered surfactant for the treatment of surfactant dificiency states.
| Ikegami, Machiko; Dhami, Rajwinder; Schuchman, Edward H (2003) Alveolar lipoproteinosis in an acid sphingomyelinase-deficient mouse model of Niemann-Pick disease. Am J Physiol Lung Cell Mol Physiol 284:L518-25 |
| Glasser, Stephan W; Detmer, Emily A; Ikegami, Machiko et al. (2003) Pneumonitis and emphysema in sp-C gene targeted mice. J Biol Chem 278:14291-8 |
| Gurel, O; Ikegami, M; Chroneos, Z C et al. (2001) Macrophage and type II cell catabolism of SP-A and saturated phosphatidylcholine in mouse lungs. Am J Physiol Lung Cell Mol Physiol 280:L1266-72 |
| Kramer, B W; Jobe, A H; Ikegami, M (2001) Exogenous surfactant changes the phenotype of alveolar macrophages in mice. Am J Physiol Lung Cell Mol Physiol 280:L689-94 |
| Rider, E D; Ikegami, M; Pinkerton, K E et al. (2000) Lysosomes from rabbit type II cells catabolize surfactant lipids. Am J Physiol Lung Cell Mol Physiol 278:L68-74 |
| Ikegami, M; Whitsett, J A; Chroneos, Z C et al. (2000) IL-4 increases surfactant and regulates metabolism in vivo. Am J Physiol Lung Cell Mol Physiol 278:L75-80 |
| Elhalwagi, B M; Zhang, M; Ikegami, M et al. (1999) Normal surfactant pool sizes and inhibition-resistant surfactant from mice that overexpress surfactant protein A. Am J Respir Cell Mol Biol 21:380-7 |
| Jobe, A H; Ikegami, M (1998) Surfactant homeostasis in corticotropin-releasing hormone deficiency in adult mice. Am J Respir Crit Care Med 158:995-7 |
| Ikegami, M; Korfhagen, T R; Whitsett, J A et al. (1998) Characteristics of surfactant from SP-A-deficient mice. Am J Physiol 275:L247-54 |
| Ikegami, M; Horowitz, A D; Whitsett, J A et al. (1998) Clearance of SP-C and recombinant SP-C in vivo and in vitro. Am J Physiol 274:L933-9 |
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