Turlej Eliza, Goszczyński Tomasz Marek, Drab Marek, Orzechowska Beata, Maciejewska Magdalena, Banach Joanna, Wietrzyk Joanna
Department of Experimental Biology, Wroclaw University of Environmental and Life Science, 50-375 Wroclaw, Poland.
Laboratory of Biomedical Chemistry, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.
J Clin Med. 2022 Apr 15;11(8):2224. doi: 10.3390/jcm11082224.
Vitamin D analogs (VDAs) may directly inhibit the growth of normal and malignant (derived from acute lymphoblastic leukemia (ALL)) B cells, as both types of cells express vitamin D receptor (VDR). We performed anti-proliferative, morphology tests and phenotyping to evaluate the sensitivity of monocytes and iDCs (immature myeloid-derived dendritic cells) on calcitriol and tacalcitol treatment, phenotyping, morphology, and size distribution measurement to determine the characteristics of microvesicles (MVs) and exosomes (EXs) derived from them and, finally, phenotyping and Elisa test to determine the effects of VDAs on modulation of the phenotype of B cells through extracellular vesicles (EVs) released by iDCs. Our results confirmed that both SC cells and iDCs were sensitive to the VDAs and showed altered surface expression of markers associated with monocyte differentiation, which was resulting in the phenotypic changes in EVs derived from them. We also showed that obtained EVs could change the morphology and phenotype of ALL-B-derived precursor cells in a different way, depending on their origin. The differential effect of VDAs on ALL-B cells, which was associated with increased or decreased expression of CD27, CD24, CD38, and CD23 expression, was observed. Hence, further studies to explain the modulation in the composition of EVs by VDAs are required.
维生素D类似物(VDAs)可能直接抑制正常和恶性(源自急性淋巴细胞白血病(ALL))B细胞的生长,因为这两种类型的细胞都表达维生素D受体(VDR)。我们进行了抗增殖、形态学测试和表型分析,以评估单核细胞和未成熟髓样来源的树突状细胞(iDCs)对骨化三醇和他骨化醇治疗的敏感性,进行表型分析、形态学和大小分布测量,以确定源自它们的微泡(MVs)和外泌体(EXs)的特征,最后进行表型分析和酶联免疫吸附测定(ELISA)测试,以确定VDAs对通过iDCs释放的细胞外囊泡(EVs)调节B细胞表型的影响。我们的结果证实,SC细胞和iDCs对VDAs均敏感,并显示与单核细胞分化相关的标志物的表面表达发生改变,这导致源自它们的EVs出现表型变化。我们还表明,根据其来源,获得的EVs可以以不同方式改变源自ALL-B的前体细胞的形态和表型。观察到VDAs对ALL-B细胞的不同作用,这与CD27、CD24、CD38和CD23表达的增加或减少有关。因此,需要进一步研究来解释VDAs对EVs组成的调节作用。