Guthmann F, Harrach-Ruprecht B, Looman A C, Stevens P A, Robenek H, Rüstow B
Department of Neonatology, Charité, Humboldt-Universität zu Berlin, Germany.
Eur J Cell Biol. 1997 Oct;74(2):197-207.
Apart from dipalmitoyl phosphatidylcholine, cholesterol is the most abundant surfactant lipid. About 90 to 99% of cholesterol of the alveolar surfactant is derived from serum lipoproteins. The aim of this study was to identify the lipoprotein which preferentially supplements type II pneumocytes with cholesterol destined for surfactant production. Ultrastructural investigations revealed that type II pneumocytes bind and take up HDL, LDL and VLDL. Binding and uptake of VLDL occurred even in the presence of excess LDL indicating that, besides LDL receptors, type II pneumocytes express additional binding sites for VLDL. Type II pneumocytes in primary culture are able to take up cholesterol added in the form of HDL, LDL and VLDL. Cholesterol uptake was lowest from HDL and highest from VLDL. The maximal velocity of cholesterol uptake from VLDL was more than three times that of cholesterol uptake from LDL. The half-maximal saturation of cholesterol uptake from VLDL was nearly half that of LDL. From these kinetic data and the distribution of free cholesterol among the serum lipoproteins, we calculated that the cholesterol uptake from VLDL is more than three times that of cholesterol uptake from LDL. In double-labeling experiments type II pneumocytes secreted palmitic acid-labeled phospholipids together with labeled free cholesterol taken up from lipoproteins. The secretion rates of both phospholipids and free cholesterol were stimulated to nearly the same extent by isoproterenol. From our results we conclude that type II pneumocytes interact specifically with HDL, LDL and VLDL. Cholesterol taken up in the form of the individual lipoproteins shows no difference in its availability for the formation of cholesterol ester and surfactant by type II pneumocytes in vitro. Based on the kinetic studies, it appears that VLDL is the major gateway through which cholesterol is provided to satisfy the cholesterol requirements of type II pneumocytes for the synthesis of surfactant.
除二棕榈酰磷脂酰胆碱外，胆固醇是含量最丰富的表面活性脂质。肺泡表面活性剂中约90%至99%的胆固醇源自血清脂蛋白。本研究的目的是确定哪种脂蛋白优先为II型肺细胞补充用于表面活性剂生成的胆固醇。超微结构研究显示，II型肺细胞能结合并摄取高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和极低密度脂蛋白（VLDL）。即使存在过量的LDL，VLDL仍能发生结合和摄取，这表明除LDL受体外，II型肺细胞还表达VLDL的其他结合位点。原代培养的II型肺细胞能够摄取以HDL、LDL和VLDL形式添加的胆固醇。从HDL摄取的胆固醇最少，从VLDL摄取的胆固醇最多。从VLDL摄取胆固醇的最大速度是从LDL摄取胆固醇最大速度的三倍多。从VLDL摄取胆固醇的半最大饱和度几乎是LDL的一半。根据这些动力学数据以及游离胆固醇在血清脂蛋白中的分布，我们计算得出从VLDL摄取的胆固醇是从LDL摄取胆固醇的三倍多。在双重标记实验中，II型肺细胞分泌棕榈酸标记的磷脂以及从脂蛋白摄取的标记游离胆固醇。异丙肾上腺素对磷脂和游离胆固醇的分泌速率的刺激程度几乎相同。从我们的结果可以得出结论，II型肺细胞与HDL、LDL和VLDL有特异性相互作用。以单个脂蛋白形式摄取的胆固醇在体外被II型肺细胞用于形成胆固醇酯和表面活性剂的可用性方面没有差异。基于动力学研究，似乎VLDL是为满足II型肺细胞合成表面活性剂对胆固醇的需求而提供胆固醇的主要途径。
