Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
PLoS One. 2020 Apr 2;15(4):e0226050. doi: 10.1371/journal.pone.0226050. eCollection 2020.
Autotaxin (ATX) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a growth factor-like signaling lysophospholipid. ATX and LPA signaling have been incriminated in the pathogenesis of different chronic inflammatory diseases and various types of cancer. In this report, deregulated ATX and LPA levels were detected in the spinal cord and plasma of mice during the development of experimental autoimmune encephalomyelitis (EAE). Among the different sources of ATX expression in the inflamed spinal cord, F4/80+ CD11b+ cells, mostly activated macrophages and microglia, were found to express ATX, further suggesting an autocrine role for ATX/LPA in their activation, an EAE hallmark. Accordingly, ATX genetic deletion from CD11b+ cells attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in neuroinflammatory disorders.
自分泌酶（ATX）是一种分泌型溶血磷脂酶 D，可催化细胞外产生溶血磷脂酸（LPA），一种类似生长因子的信号溶血磷脂。ATX 和 LPA 信号已被牵连到不同慢性炎症性疾病和各种类型的癌症的发病机制中。在本报告中，在实验性自身免疫性脑脊髓炎（EAE）发展过程中，在小鼠脊髓和血浆中检测到失调的 ATX 和 LPA 水平。在炎症性脊髓中的 ATX 表达的不同来源中，发现 F4/80+ CD11b+ 细胞（主要为激活的巨噬细胞和小胶质细胞）表达 ATX，这进一步表明 ATX/LPA 在其激活中具有自分泌作用，这是 EAE 的一个标志。相应地，从 CD11b+细胞中敲除 ATX 减轻了 EAE 的严重程度，因此提出了 ATX/LPA 轴在神经炎症性疾病中的致病作用。
