Ueda T, Ikegami M, Jobe A
Department of Pediatrics, Harbor-UCLA Medical Center, University of California, Los Angeles School of Medicine, Torrance 90509.
Am J Respir Crit Care Med. 1994 May;149(5):1254-9. doi: 10.1164/ajrccm.149.5.8173767.
Surfactant in the alveolar space can be separated into heavy and light subtypes by differential centrifugation or on isopyknic sucrose density gradients. The conversion from heavy subtypes to light subtypes occurs in vitro by surface-area cycling. However, the function of light subtypes made by cycling and substances that might influence in vitro conversion have not been evaluated. Therefore, we compared the in vivo function of the heavy and light subtypes isolated from rabbit surfactant and similar density fractions prepared in vitro by surface-area cycling. We then asked if serum, globulin, or albumin would alter the in vitro conversion. The function of surfactant fractions was studied in vivo by treating surfactant-deficient 27 d gestational age preterm rabbits with 50 mg/kg of heavy or light subtype surfactant. Dynamic compliance values and lung volumes from PV curve measurements showed that heavy subtypes had superior in vivo function compared with light subtypes independent of in vivo or in vitro sources (p < 0.01). Light subtypes prepared in vitro lost surfactant function and were similar to in vivo light forms. When serum proteins were added to the heavy subtype surfactant, the conversion rate from heavy to light subtypes was accelerated. Serum accelerated conversion more than globulin, and the serine proteinase inhibitor diisopropylfluorophosphate blocked the conversion. Albumin had no significant effect. The increased rate of conversion caused by serum identifies a new mechanism for surfactant inactivation that could occur with lung injuries associated with increased alveolar protein.
肺泡腔内的表面活性剂可通过差速离心或在等密度蔗糖密度梯度上分离为重亚型和轻亚型。在体外，通过表面积循环，重亚型可转化为轻亚型。然而，通过循环产生的轻亚型的功能以及可能影响体外转化的物质尚未得到评估。因此，我们比较了从兔表面活性剂中分离出的重亚型和轻亚型以及通过表面积循环在体外制备的类似密度组分的体内功能。然后，我们研究血清、球蛋白或白蛋白是否会改变体外转化。通过用50mg/kg的重亚型或轻亚型表面活性剂治疗27天胎龄的表面活性剂缺乏早产兔，在体内研究表面活性剂组分的功能。来自压力-容积曲线测量的动态顺应性值和肺容积表明，与轻亚型相比，重亚型具有更好的体内功能，与体内或体外来源无关（p<0.01）。体外制备的轻亚型失去了表面活性剂功能，与体内轻形式相似。当将血清蛋白添加到重亚型表面活性剂中时，从重亚型到轻亚型的转化率加快。血清比球蛋白更能加速转化，丝氨酸蛋白酶抑制剂二异丙基氟磷酸酯可阻断这种转化。白蛋白没有显著影响。血清引起的转化率增加确定了一种新的表面活性剂失活机制，这种机制可能发生在与肺泡蛋白增加相关的肺损伤中。
