SUSCEPTIBILITY OF EXOGENOUS SURFACTANT TO PHOSPHOLIPASE A(2) DEGRADATION

The inhibition of surfactant biophysical activity in vivo is potential ly mediated by many factors, including serum proteins, particularly en zymatic proteins such as phospholipases. In the present study, we inve stigated the susceptibility of the phosphatidylcholine component of tw o exogenous surfactants, Exosurf(R) and Survanta(R), to secretory-type phospholipase A(2) (PLA(2)) deacylation in vitro. Lyophilized Exosurf and Survanta preparations were incubated at 37 degrees C for 120 min in the presence of bovine pancreatic PLA(2), and the production of lys ophosphatidylcholine was determined as a measure of the magnitude of p hosphatidylcholine deacylation. The phosphatidylcholine component of S urvanta was readily deacylated by PLA(2), whereas the dipalmitoylphosp hatidycholine (DPPC) component of Exosurf was resistant over the entir e duration of the assay. To further evaluate this observed resistance the individual and combined effects of tyloxapol and hexadecanol, comp onents of Exosurf, upon PLA(2) deacylation of Survanta and DPPC were i nvestigated. In both Survanta and DPPC preparations, PLA(2)-mediated d eacylation was significantly inhibited in the presence of tyloxapol. W e conclude that the presence of tyloxapol in the Exosurf preparation i nhibits secretory type PLA(2) mediated DPPC deacylation. This unique f eature of Exosurf may be of clinical significance when this preparatio n is utilized in the treatment of surfactant-deficient infants.