Yatomi Yutaka
Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Rinsho Byori. 2010 Jun;58(6):631-5.
The lysophospholipid mediator lysophosphatidic acid (LPA) has been shown to elicit a variety of (patho) physiological responses through specific cell-surface G protein-coupled receptors, which are now considered as promising targets for therapeutic purposes. On the other hand, determination of their concentrations in human samples, especially plasma, is clinically relevant and important for diagnostic purposes since these lysophospholipids mainly act extracellularly. LPA is predominantly and continuously produced in blood from lysophosphatidylcholine (LPC) through the plasma lysophospholipase D (lysoPLD) activity of autotaxin (ATX). Since the enzyme lysoPLD/ATX and its substrate LPC co-exist in the plasma, the level of plasma LPA changes easily in vitro after venepuncture. Laboratory testing of LPA for clinical purposes can be conducted reliably only when the samples are prepared under stringent conditions. Although it is postulated that LPA undergoes extensive dephosphorylation in vivo due to the action of lipid phosphate phosphatase, multiple regression analysis showed a strong positive correlation between the plasma LPA concentration and serum lysoPLD/ATX level. Since the serum ATX antigen level is stable, i.e., the preparation of clinical samples for this ATX measurement is easy and since its level is closely correlated to the plasma LPA concentration, the ATX assay seems to be promising for laboratory testing. In fact, the ATX level is significantly increased in several disorders, including chronic liver diseases and malignant lymphoma. The clinical significance of the LPA and lysoPLD/ATX assays will be discussed.
溶血磷脂介质溶血磷脂酸(LPA)已被证明可通过特定的细胞表面G蛋白偶联受体引发多种(病理)生理反应,这些受体现在被认为是有前景的治疗靶点。另一方面,测定其在人体样本尤其是血浆中的浓度在临床上具有相关性且对诊断很重要,因为这些溶血磷脂主要在细胞外起作用。LPA主要通过自分泌运动因子(ATX)的血浆溶血磷脂酶D(lysoPLD)活性由溶血磷脂酰胆碱(LPC)在血液中持续产生。由于lysoPLD/ATX酶及其底物LPC共存于血浆中,静脉穿刺后血浆LPA水平在体外容易发生变化。只有在严格条件下制备样本时,才能可靠地进行用于临床目的的LPA实验室检测。尽管据推测LPA在体内由于脂质磷酸酶的作用会经历广泛的去磷酸化,但多元回归分析显示血浆LPA浓度与血清lysoPLD/ATX水平之间存在强正相关。由于血清ATX抗原水平稳定,即用于该ATX测量的临床样本制备容易,且其水平与血浆LPA浓度密切相关,ATX测定似乎有望用于实验室检测。事实上,在包括慢性肝病和恶性淋巴瘤在内的几种疾病中,ATX水平显著升高。将讨论LPA和lysoPLD/ATX测定的临床意义。