Cysteinyl-leukotrienes (cys-LTs) have well-characterized physiopathological roles in the development of inflammatory diseases. We have previously found that protein tyrosine phosphatase ε (PTPε) is a signaling partner of CysLT1R, a high affinity receptor for leukotriene D4 (LTD4). There are two major isoforms of PTPε, receptor-like (RPTPε) and cytoplasmic (cyt-)PTPε, both of which are encoded by the PTPRE gene but from different promoters. In most cells, their expression is mutually exclusive, except in human primary monocytes, which express both isoforms. Here, we show differential PTPε isoform expression patterns between monocytes, M1 and M2 human monocyte-derived macrophages (hMDMs), with the expression of glycosylated forms of RPTPε predominantly in M2-polarized hMDMs. Using PTPε-specific siRNAs and expression of RPTPε and cyt-PTPε, we found that RPTPε is involved in monocyte adhesion and migration of M2-polarized hMDMs in response to LTD4 Altered organization of podosomes and higher phosphorylation of the inhibitory Y-722 residue of ROCK2 was also found in PTPε-siRNA-transfected cells. In conclusion, we show that differentiation and polarization of monocytes into M2-polarized hMDMs modulates the expression of PTPε isoforms and RPTPε is involved in podosome distribution, ROCK2 activation and migration in response to LTD4.

中文翻译：

---

RPTPε 通过 ROCK2 信号传导和足体形成促进 M2 极化巨噬细胞迁移。

半胱氨酰白三烯 (cys-LTs) 在炎症性疾病的发展中具有明确的生理病理学作用。我们之前发现蛋白酪氨酸磷酸酶 ε (PTPε) 是 CysLT1R 的信号伙伴，CysLT1R 是白三烯 D4 (LTD4) 的高亲和力受体。PTPε 有两种主要的亚型，受体样 (RPTPε) 和细胞质 (cyt-)PTPε，两者均由 PTPRE 基因编码，但来自不同的启动子。在大多数细胞中，它们的表达是相互排斥的，除了在表达两种同种型的人原代单核细胞中。在这里，我们展示了单核细胞、M1 和 M2 人单核细胞衍生的巨噬细胞 (hMDM) 之间的差异 PTPε 亚型表达模式，其中糖基化形式的 RPTPε 主要在 M2 极化的 hMDM 中表达。使用 PTPε 特异性 siRNA 和 RPTPε 和 cyt-PTPε 的表达，我们发现 RPTPε 参与响应 LTD4 的 M2 极化 hMDM 的单核细胞粘附和迁移。 在 PTPε-siRNA 转染的细胞中也发现了 ROCK2 的抑制性 Y-722 残基的更高磷酸化的足小体组织和更高的磷酸化。总之，我们表明单核细胞分化和极化为 M2 极化 hMDM 可调节 PTPε 同种型的表达，并且 RPTPε 参与响应于 LTD4 的足体分布、ROCK2 激活和迁移。