Mallampalli R K, Salome R G, Bowen S L, Chappell D A
Department of Internal Medicine, Department of Veterans Affairs Medical Center, The University of Iowa College of Medicine, Iowa City 52242, USA.
J Clin Invest. 1997 Apr 15;99(8):2020-9. doi: 10.1172/JCI119370.
Surfactant synthesis is critically dependent on the availability of fatty acids. One fatty acid source may be circulating triglycerides that are transported in VLDL, and hydrolyzed to free fatty acids by lipoprotein lipase (LPL). To evaluate this hypothesis, we incubated immortalized or primary rat alveolar pre-type II epithelial cells with VLDL. The cells were observed to surface bind, internalize, and degrade VLDL, a process that was induced by exogenous LPL. LPL induction of lipoprotein uptake significantly increased the rates of choline incorporation into phosphatidylcholine (PC) and disaturated PC, and these effects were associated with a three-fold increase in the activity of the rate-regulatory enzyme for PC synthesis, cytidylyltransferase. Compared with native LPL, a fusion protein of glutathione S-transferase with the catalytically inactive carboxy-terminal domain of LPL did not activate CT despite inducing VLDL uptake. A variant of the fusion protein of glutathione S-transferase with the catalytically inactive carboxy-terminal domain of LPL that partially blocked LPL-induced catabolism of VLDL via LDL receptors also partially blocked the induction of surfactant synthesis by VLDL. Taken together, these observations suggest that both the lipolytic actions of LPL and LPL-induced VLDL catabolism via lipoprotein receptors might play an integral role in providing the fatty acid substrates used in surfactant phospholipid synthesis.
表面活性剂的合成严重依赖于脂肪酸的供应。一种脂肪酸来源可能是在极低密度脂蛋白（VLDL）中运输的循环甘油三酯，其被脂蛋白脂肪酶（LPL）水解为游离脂肪酸。为了评估这一假设，我们将永生化或原代大鼠肺泡II型前上皮细胞与VLDL一起孵育。观察到细胞可与VLDL发生表面结合、内化并降解，这一过程由外源性LPL诱导。LPL诱导脂蛋白摄取显著提高了胆碱掺入磷脂酰胆碱（PC）和二饱和PC的速率，这些效应与PC合成的速率调节酶胞苷转移酶的活性增加三倍相关。与天然LPL相比，谷胱甘肽S-转移酶与LPL催化无活性的羧基末端结构域的融合蛋白尽管诱导了VLDL摄取，但并未激活CT。谷胱甘肽S-转移酶与LPL催化无活性的羧基末端结构域的融合蛋白变体，其通过低密度脂蛋白受体部分阻断LPL诱导的VLDL分解代谢，也部分阻断了VLDL对表面活性剂合成的诱导。综上所述，这些观察结果表明，LPL的脂解作用以及LPL通过脂蛋白受体诱导的VLDL分解代谢可能在提供用于表面活性剂磷脂合成的脂肪酸底物方面发挥不可或缺的作用。
