Lungs, surfactant

Surfactants play an important role in the lungs because they provide a mechanism to prevent droplets of water from blocking the narrow airways of the pulmonary system. By lowering the surface tension of fluids 

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Discuss the role of the various components of lung surfactants in making a resilient film. 

Beneficial effects have also been attributed to PAF. In reproduction, PAF secreted by the fertilized egg is instrumental in the implantation of the egg in the uterine wall. PAF is produced in significant quantities in the lungs of the fetus late in pregnancy and may stimulate the production of fetal lung surfactant, a protein-lipid complex that prevents collapse of the lungs in a newborn infant. 

The well-defined helical structure associated with appropriately substituted peptoid oligomers (Section 1.6) can be employed to fashion compounds that closely mimic the stracture and function of certain bioactive peptides. There are many examples of small helical peptides (<100 residues) whose mimicry by non-natural ohgomers could potentially yield valuable therapeutic and bioactive compounds. This section describes peptoids that have been rationaUy designed as mimics of antibacterial peptides, lung surfactant proteins, and coUagen proteins. Mimics of HIV-Tat protein, although relevant to this discussion, were described previously in this chapter (Sections 1.3.2 and 1.4.1). 

Peptoid-Based Mimics of Lung Surfactant Proteins... 

There is a clinical need for non-natural, functional mimics of the lung surfactant (LS) proteins B and C (SP-B and SP-C), which could be used in a biomimetic LS replacement to treat respiratory distress syndrome (RDS) in premature infants [56]. An effective surfactant replacement must meet the following performance requirements (i) rapid adsorption to the air-liquid interface, (ii) re-spreadabihty... 

Rouhi, A.M. a peptoid promise Synthetic lung surfactant mimics may widen access to treatment of respiratory disease. Chem. Eng. News 2001, 79, 50-51. 

Gericke, a., Flach, C. R., and Mendelsohn, R. Structure and orientation of lung surfactant SP-C and L-alpha-dipalmitoyl-phosphatidylcholine in aqueous mono-layers. Biophys.J. 1997, 73, 492-499. 

Lipp, M.M., Lee, K.Y.C., Waring, A., and Zasadzinski, J.A. Fluorescence, polarized fluorescence, and Brewster angle microscopy of palmitic acid and lung surfactant protein B monolayers. Biophys. J. 1997, 72, 2783-2804. 

Seurynck, S.L., Johnson, M., and Barron, A. E. Simple helical peptoid analogues of lung surfactant protein B. 2003. (Manuscript in preparation). 

For the treatment of lung surfactant deficiency in premature human infants suffering from respiratory distress syndrome, limited clinical trials were performed showing that liposomes in the lung-instilled intratracheally either as an aerosolized mist (Ivey et al., 1977) or as a suspension via an endotracheal tube (Fujiwara et al., 1980)—rapidly improved lung function. No adverse effects were observed as a result of the supplementation with surfactant-like material. It appears, therefore, that liposomes are a suitable system for the delivery of major phospholipid components of endogenous lung surfactant. 

Deficiency of Lung Surfactant Causes Respiratory Distress Syndrome... 

Lung surfactant is composed mainly of lipid with some proteins and carbohydrate and prevents the alveoli from collapsing. Surfactant activity is largely attributed to dipalmitoylphosphatidylcholine, which is synthesized shortly before parturition in full-term infants. Deficiency of lung surfactant in the lungs of many preterm newborns gives rise to respiratory distress syndrome. Administration of either natural or artificial surfactant has been of therapeutic benefit. 

Phospholipids and sphingolipids are involved in several disease processes, including respiratory distress syndrome (lack of lung surfactant), multiple sclerosis... 

Green FHY, Schurch S, De Sanctis GT, et al. 1991. Effects of hydrogen sulfide exposure on surface properties of lung surfactant. J Appl Physiol 70 1943-1949. 

Within 24 h, lung surfactant decreased 32%, suggesting a loss in alveolar stability (Haley 1979)... 

Shelley, S.A., Oxidant-induced alterations of lung surfactant system, J. Fla. Med. Assoc. 

Guillot, L., et al., Cutting edge The immunostimulatory activity of the lung surfactant protein-A involves Toll-like receptor 4, J. Immunol. 168, 12, 5989, 2002. 

Wiedmann TS, Bhatia R, Wattenberg LW (2000) Drug solubilization in lung surfactant. J Control Release 65 43 47. 

Veldhuizen R, Possmayer F (2004) Phospholipid metabolism in lung surfactant. Subcell Biochem 37 359-388... 

Balis JU, Bumgarner SD, Paciga JE, Paterson JF, Shelley SA (1984) Synthesis of lung surfactant-associated glycoproteins by A549 cells description of an in vitro model for human type II cell dysfunction. Exp Lung Res 6(3-4) 197-213... 

The situation is, however, different in the alveolar region of the lung where the respiratory gas exchange takes place. Its thin squamous epithelium is covered by the so-called alveolar surface liquid (ASL). Its outermost surface is covered by a mixture of phospholipids and proteins with a low surface tension, also often referred to as lung surfactant. For this surfactant layer only, Scarpelli et al. [74] reported a thickness between 7 and 70 nm in the human lung. For the thickness of an additional water layer in between the apical surface of alveolar epithelial cells and the surfactant film no conclusive data are available. Hence, the total thickness of the complete ASL layer is actually unknown, but is certainly thinner than 1 gm. 

Notter RH, Shapiro DL. Lung surfactants for replacement therapy biochemical, biophysical, and clinical aspects. Clin Perinatol 1987 14(3) 433-479. 

Oosterlaken-Dijksterhuis MA, Haagsman HP, van Golde LM, et al. Characterization of lipid insertion into monomolecular layers mediated by lung surfactant proteins SP-B and SP-C. Biochemistry 1991 30(45) 10965-10971. 

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