Department of Human Physiology, University of Oregon, 122c Esslinger Hall, Eugene, OR, 97403, USA.
Department of Medicine and Pharmacology, Medical University of Vienna, 1090, Vienna, Austria.
Lipids Health Dis. 2018 May 28;17(1):127. doi: 10.1186/s12944-018-0769-6.
Previous studies of lipoproteins in patients with sepsis have been performed on density fractions isolated by conventional ultracentrifugation that are heterogeneous and provide no information about the cargo of apoproteins present in the immunochemically distinct subclasses that populate the density classes. Since apoproteins are now known to have important roles in host defense, we have separated these subclasses according to their apoprotein content and characterized their changes during experimental endotoxemia in human volunteers.
We have studied apoB- and apoA containing lipoprotein subclasses in twelve healthy male volunteers before and for 8 h after a single dose of endotoxin (ET; 2 μg/kg) to stimulate inflammation.
After endotoxin, TG, TC, apoB and the apoB-containing lipoprotein cholesterol-rich subclass LpB and two of the three triglyceride-rich subclasses (TGRLP: Lp:B:C, LpB:C:E+ LpB:E) all declined. In contrast, the third TGRLP, LpA-II:B:C:D:E ("complex particle"), after reaching a nadir at 4 h rose 49% above baseline, p = .006 at 8 h and became the dominant particle in the TGRLP pool. This increment exceeds the threshold of > 25% change required for designation as an acute phase protein. Simultaneous decreases in LpA-I:A-II and LpB:C:E + LpB:E suggest that these subclasses undergo post-translational modification and contribute to the formation of new LpA-II:B:C:D:E particles.
We have identified a new acute phase lipoprotein whose apoprotein constituents have metabolic and immunoregulatory properties applicable to host defense that make it well constituted to engage in the APR.
先前对脓毒症患者脂蛋白的研究是在通过传统超速离心分离的密度级分上进行的，这些级分是不均匀的，并且不能提供有关存在于免疫化学上不同亚类中的载脂蛋白的货物信息，这些亚类填充了密度级分。由于现在已知载脂蛋白在宿主防御中具有重要作用，因此我们根据载脂蛋白含量对这些亚类进行了分离，并在人类志愿者的实验性内毒素血症期间对其变化进行了特征描述。
我们在十二名健康男性志愿者中研究了载脂蛋白 B 和载脂蛋白 A 所含脂蛋白亚类，这些志愿者在单次给予内毒素（ET；2μg/kg）刺激炎症之前和之后 8 小时进行了研究。
内毒素后，TG、TC、apoB 和富含载脂蛋白 B 的脂蛋白胆固醇丰富的亚类 LpB 以及三个甘油三酯丰富的亚类中的两个（TGRLP：Lp:B:C、LpB:C:E+LpB:E）均下降。相比之下，第三个 TGRLP，LpA-II:B:C:D:E（“复合颗粒”），在 4 小时达到最低点后，在 8 小时时比基线升高 49%，p=0.006，并且成为 TGRLP 池中的主要颗粒。这种增加超过了指定为急性相蛋白所需的>25%变化的阈值。LpA-I:A-II 和 LpB:C:E+LpB:E 的同时减少表明这些亚类经历了翻译后修饰，并有助于新的 LpA-II:B:C:D:E 颗粒的形成。
我们已经确定了一种新的急性相脂蛋白，其载脂蛋白成分具有代谢和免疫调节特性，适用于宿主防御，使其能够很好地参与 APR。
