The goal of this study is to gain a better understanding of pulmonary surfactant using x-ray and neutron diffraction methods on model and native surfactants. This is the first time x-ray and neutron diffraction will be used to probe the monolayer structure of both model and native surfactant in vitro. We expect that the data obtained from this study will help us formulate a model (at the molecular level) which explains how the, various components of pulmonary surfactant interact to lower the alveolar surface tension.! Thus, the results of this study could aid in the design of surfactants for replacement therapy. Surfactant is a complex mixture of phospholipid, neutral lipid, glycolipid and protein. It lines the inner surface of the alveoli and is required for normal pulmonary function. In this context, quantitative and/or qualitative alterations of lung surfactant in such human pulmonary conditions as respiratory distress syndrome(RDS), adult respiratory distress syndrome (ARDS) and pulmonary alveolar proteinosis (PAP) contribute significantly to eventual morbidity and mortality. We first propose to study model surfactants. The simplest model surfactant will be composed of a single two or three component lipid system (ie. DPPC/PG [70-80:30-20], DPPC/Cholesterol, etc.) with the addition of apoprotein SP-B and/or SP-C. The model surfactant will be spread on a Langmuir film balance and Langmuir-Blodgett mono/multilayer films will be fabricated at various surface pressures. Scattering from the Langmuir-Blodgett films will be measured and both profile and in-plane structures determined for the surfactant. To better approximate in vivo conditions, x-ray scattering from the surfactant film, while spread on the Langmuir balance, will be directly measured. The surface pressure will be varied so that its effect on surfactant structure at the airwater interface can be studied. Model surfactant studies are only a first approximation to native surfactant. Native surfactant will be isolated from healthy rats, from which the various lipid components. will be isolated. Studies similar to the model studies outlined above will be repeated on the native surfactant and its components.
|Swendsen, C L; Skita, V; Thrall, R S (1996) Alterations in surfactant neutral lipid composition during the development of bleomycin-induced pulmonary fibrosis. Biochim Biophys Acta 1301:90-6|
|Skita, V; Chester, D W; Oliver, C J et al. (1995) Bilayer characteristics of a diether phosphonolipid analog of the major lung surfactant glycerophospholipid dipalmitoyl phosphatidylcholine. J Lipid Res 36:1116-27|
|Young, H S; Skita, V; Mason, R P et al. (1992) Molecular basis for the inhibition of 1,4-dihydropyridine calcium channel drugs binding to their receptors by a nonspecific site interaction mechanism. Biophys J 61:1244-55|