Lissandrini Daniele, Vermi William, Vezzalini Marzia, Sozzani Silvano, Facchetti Fabio, Bellone Graziella, Mafficini Andrea, Gentili Francesca, Ennas Maria Grazia, Tecchio Cristina, Sorio Claudio
Department of Pathology, University of Verona, Verona, Italy.
Blood. 2006 Dec 15;108(13):4223-31. doi: 10.1182/blood-2006-05-024257. Epub 2006 Aug 8.
Protein tyrosine phosphatase (PTPgamma) is a receptor-like molecule with a known role in murine hematopoiesis. We analyzed the regulation of PTPgamma expression in the human hematopoietic system, where it was detected in human peripheral blood monocytes and dendritic cells (DCs) of myeloid and plasmacytoid phenotypes. Its expression was maintained during in vitro monocyte differentiation to dendritic cells (moDC) and was further increased after maturation with bacterial lipopolysaccharide (LPS), CD40L, and TNFalpha. But PTPgamma was absent when monocytes from the same donor were induced to differentiate in macrophages. B and T lymphocytes did not express PTPgamma. Rather, PTPgamma mRNA was expressed in primary and secondary lymphoid tissues, and the highest expression was in the spleen. PTPgamma was detected by immunohistochemistry in subsets of myeloid-derived DCs and specialized macrophages (tingible bodies, sinus and alveolar macrophages). Classic macrophages in infective or reactive granulomatous reactions did not express PTPgamma. Increased PTPgamma expression was associated with a decreased ability to induce proliferation and interferon-gamma secretion in T cells by moDCs from patients with advanced pancreatic cancer. Taken together, these results indicate that PTPgamma is a finely regulated protein in DC and macrophage subsets in vitro and in vivo.
蛋白酪氨酸磷酸酶(PTPγ)是一种受体样分子,在小鼠造血过程中发挥着已知作用。我们分析了人造血系统中PTPγ表达的调控情况,在人外周血单核细胞以及髓样和浆细胞样表型的树突状细胞(DC)中检测到了该分子。在体外单核细胞向树突状细胞(moDC)分化过程中,其表达得以维持,并且在用细菌脂多糖(LPS)、CD40L和TNFα使其成熟后表达进一步增加。但是,当诱导来自同一供体的单核细胞分化为巨噬细胞时,PTPγ并不存在。B淋巴细胞和T淋巴细胞不表达PTPγ。相反,PTPγ mRNA在一级和二级淋巴组织中表达,其中脾脏中的表达最高。通过免疫组织化学在髓样来源的DC亚群和特殊巨噬细胞(核内体、窦和肺泡巨噬细胞)中检测到了PTPγ。感染性或反应性肉芽肿反应中的典型巨噬细胞不表达PTPγ。晚期胰腺癌患者的moDC诱导T细胞增殖和分泌干扰素-γ的能力下降与PTPγ表达增加有关。综上所述,这些结果表明PTPγ在体外和体内的DC和巨噬细胞亚群中是一种受到精细调控的蛋白。