Sharapova T N, Romanova E A, Sashchenko L P, Yashin D V
Institute of Gene Biology of the Russian Academy of Sciences, Vavilova Str., 34/5, Moscow, 119334 , Russia.
Acta Naturae. 2018 Oct-Dec;10(4):115-120.
The discovery of new chemokines that induce the migration of lymphocytes to the infection site is important for the targeted search for therapeutic agents in immunotherapy. We recently showed that Tag7 (PGLYRP1), an innate immunity protein, forms a stable complex with the Ca -binding protein Mts1 (S100A4), which is able to induce lymphocyte movement, although the individual Tag7 and Mts1 do not have this activity. The purpose of this study is to identify receptors that induce the migration of lymphocytes along the concentration gradient of the Tag7-Mts1 complex, and the components of this complex capable of interacting with these receptors. The study investigated the migration of human PBMC under the action of the Tag7-Mts1complex. PBMC of healthy donors were isolated using a standard Ficoll-Hypaque gradient centrifugation procedure. It has been established that the movement of PBMC along the concentration gradient of the Tag7-Mts1 complex is induced by the classical chemotactic receptors CCR5 and CXCR3. It has been shown that only Mts1 is able to bind to the extracellular domain of CCR5, however, this binding is not enough to induce cell movement. A comparative analysis of the primary and 3D structures of the three proteins revealed the homology of the amino acid sequence fragments of the Tag7-Mts1 protein complex with different sites of the CCR5 receptor ligand - MIP1α protein. In conclusion, it should be noted that the Tag7-Mts1 complex can be considered as a new ligand of the classical chemotactic receptors CCR5 and CXCR3.
发现能够诱导淋巴细胞迁移至感染部位的新型趋化因子，对于在免疫疗法中靶向寻找治疗药物至关重要。我们最近发现，固有免疫蛋白Tag7（PGLYRP1）与钙结合蛋白Mts1（S100A4）形成稳定复合物，该复合物能够诱导淋巴细胞移动，尽管单独的Tag7和Mts1不具备此活性。本研究的目的是鉴定能够沿着Tag7-Mts1复合物浓度梯度诱导淋巴细胞迁移的受体，以及该复合物中能够与这些受体相互作用的成分。该研究调查了Tag7-Mts1复合物作用下人外周血单核细胞（PBMC）的迁移情况。采用标准的Ficoll-Hypaque梯度离心法分离健康供体的PBMC。已证实，PBMC沿着Tag7-Mts1复合物浓度梯度的移动是由经典趋化受体CCR5和CXCR3诱导的。已表明只有Mts1能够与CCR5的胞外结构域结合，然而，这种结合不足以诱导细胞移动。对这三种蛋白质的一级结构和三维结构进行比较分析，揭示了Tag7-Mts1蛋白复合物的氨基酸序列片段与CCR5受体配体-MIP1α蛋白不同位点的同源性。总之，应当指出，Tag7-Mts1复合物可被视为经典趋化受体CCR5和CXCR3的新配体。
