Duncan J E, Hatch G M, Belik J
Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Can J Physiol Pharmacol. 1996 Aug;74(8):957-63.
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.
体内表面活性剂生物物理活性的抑制可能由多种因素介导，包括血清蛋白，特别是酶蛋白，如磷脂酶。在本研究中，我们在体外研究了两种外源性表面活性剂Exosurf和Survanta的磷脂酰胆碱成分对分泌型磷脂酶A2（PLA2）脱酰作用的敏感性。将冻干的Exosurf和Survanta制剂在牛胰PLA2存在下于37℃孵育120分钟，并测定溶血磷脂酰胆碱的产生，作为磷脂酰胆碱脱酰程度的指标。Survanta的磷脂酰胆碱成分很容易被PLA2脱酰，而Exosurf的二棕榈酰磷脂酰胆碱（DPPC）成分在整个测定过程中具有抗性。为了进一步评估这种观察到的抗性，研究了Exosurf的成分tyloxapol和十六醇对Survanta和DPPC的PLA2脱酰作用的单独和联合影响。在Survanta和DPPC制剂中，tyloxapol的存在均显著抑制了PLA2介导的脱酰作用。我们得出结论，Exosurf制剂中tyloxapol的存在抑制了分泌型PLA2介导的DPPC脱酰作用。当该制剂用于治疗表面活性剂缺乏的婴儿时，Exosurf的这一独特特性可能具有临床意义。
