Surfactant, the surface-active material which imparts mechanical stability to alveoli at low lung volumes, has a complex intrapulmonary metabolic life cycle including biosynthesis, secretion, recycling, and catabolism. These events are related and subject to as yet unidentified control mechanisms which result in well regulated alveolar surfactant pool sizes that differ between adult and young animals. The major metabolic variable which changes with development appears to be the difference in catabolic activity within the lung. However, the intrapulmonary catabolic pathways remain poorly understood. The overall goal of the studies in this proposal is to systematically define surfactant phospholipid catabolic pathways at cellular and subcellular levels within the lung and determine developmentally related changes in these pathways. To accomplish this, dipalmitoylphosphatidylcholine ether (DPC ether), a poorly catabolized analog of the major surfactant phospholipid (DPC) but with similar alveolar clearance behavior, will be used to probe catabolic activities in the lungs of developing and adult animals. The studies will document the central role of the type II cell in cellular processing of surfactant and, subsequently, will localize the catabolic pathways within specific intracellular organelles. The lysosomes are felt to play a key role in these catabolic events and methods have been developed by Dr. Rider for isolation of these organelles from lung tissue. The fractionation procedures will then be adapted for and applied to primary isolates of type II cells. Understanding these basic cellular events involved in processing of surfactant phospholipids is important, particularly in this era of surfactant replacement therapy.
| Holmes, G M; Chapple, W D; Leipheimer, R E et al. (1991) Electromyographic analysis of male rat perineal muscles during copulation and reflexive erections. Physiol Behav 49:1235-46 |
