Date of Award
Doctor of Philosophy
Pulmonary surfactant stabilizes the lung by reducing the surface tension at the air liquid interface of the alveolus. Phosphatidylcholine represents the principal component of surfactant (70% by weight), other lipids account for 20% of surfactant and the remaining 10% is protein. Four surfactant-associated proteins have been identified, surfactant associated protein (SP) SP-A, SP-B, SP-C and SP-D.;This thesis describes the investigations on the following aspects of surfactant metabolism: (1) phosphatidylcholine synthesis, (2) alterations in surfactant after lung transplantation and (3) mechanisms of alveolar surfactant subtype conversion.;(1) The de novo synthesis of acyl-specific phosphatidylcholine via the acylation of glycerol-3-phosphocholine (GPC) has been investigated in lung and liver. Attempts to acylate radioactive GPC were unsuccessful. It appears the previously reported evidence in favour of the GPC dependent pathway was based on inaccurate identification of radioactive products. In liver, glycerol and glucose were identified as the true reaction products. Lung also formed some glycerol and another unidentified product which was shown not to be GPC. (2) In many types of lung injury, respiratory failure is associated with alterations in pulmonary surfactant. Prolonged storage of a donor lung before transplantation leads to respiratory failure after reperfusion. Analysis of lung lavage after transplantation revealed several alterations in surfactant; phosphatidylglycerol was decreased, sphingomyelin was increased, SP-A was decreased and the ratio of large to small surfactant aggregates was increased. Furthermore, the amount of blood proteins in lung lavage was increased. It was concluded that the effects of surfactant supplementation in lung transplantation should be investigated. (3) The large surfactant aggregate subtype, obtained as a 40,000g pellet after centrifugation of lung lavage, can be converted to the small surfactant aggregate subtype by an in vitro method known as surface area cycling. Subtype conversion leads to the degradation of SP-B, as demonstrated by dot blot analysis, resulting in a loss of biophysical activity. It is proposed that this degradation occurs during lipid adsorption initiated by a changing surface area.;Surface area cycling of different surfactant preparations led to the conclusion that SP-A and SP-B are necessary for large aggregate integrity.
Veldhuizen, Rudolf A., "Aspects Of Pulmonary Surfactant Metabolism" (1993). Digitized Theses. 2201.