Susceptibility of exogenous surfactant to phospholipase A2 degradation.
The inhibition of surfactant biophysical activity in vivo is potentially mediated by many factors, including serum proteins, particularly enzymatic proteins such as phospholipases. In the present study, we investigated the susceptibility of the phosphatidylcholine component of two exogenous surfactants, Exosurf and Survanta, to secretory-type phospholipase A2 (PLA2) deacylation in vitro. Lyophilized Exosurf and Survanta preparations were incubated at 37 degrees C for 120 min in the presence of bovine pancreatic PLA2, and the production of lysophosphatidylcholine was determined as a measure of the magnitude of phosphatidylcholine deacylation. The phosphatidylcholine component of Survanta was readily deacylated by PLA2, whereas the dipalmitoylphosphatidycholine (DPPC) component of Exosurf was resistant over the entire duration of the assay. To further evaluate this observed resistance the individual and combined effects of tyloxapol and hexadecanol, components of Exosurf, upon PLA2 deacylation of Survanta and DPPC were investigated. In both Survanta and DPPC preparations, PLA2-mediated deacylation was significantly inhibited in the presence of tyloxapol. We conclude that the presence of tyloxapol in the Exosurf preparation inhibits secretory type PLA2 mediated DPPC deacylation. This unique feature of Exosurf may be of clinical significance when this preparation is utilized in the treatment of surfactant-deficient infants.
Duncan
J E
JE
Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Hatch
G M
GM
Belik
J
J
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000107:Acetylation; D000818:Animals; D001688:Biological Products; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008244:Lysophosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics
D001688:Biological Products; D004338:Drug Combinations; D005233:Fatty Alcohols; D008244:Lysophosphatidylcholines; D011663:Pulmonary Surfactants; D010767:Phosphorylcholine; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; C005031:cetyl alcohol; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; D010741:Phospholipases A; D054467:Phospholipases A2; C072197:beractant; C016811:tyloxapol