Pedra Joao H F, Sukumaran Bindu, Carlyon Jason A, Berliner Nancy, Fikrig Erol
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, The Anlyan Center for Medical Research and Education, 300 Cedar St., Room 525A P.O. Box 208031, New Haven, CT 06520-8031, USA.
Genomics. 2005 Sep;86(3):365-77. doi: 10.1016/j.ygeno.2005.05.008.
Anaplasma phagocytophilum is a gram-negative obligate intracellular bacterium that persists within neutrophils. We assessed the impact of A. phagocytophilum infection in NB4 promyelocytic leukemic cells using high-density oligoarray, two-dimensional differential gel electrophoresis and liquid chromatography-mass spectrometry. Our Affymetrix data revealed that A. phagocytophilum altered the expression of transcription factors, cell adhesion molecules, signal transduction genes, and proinflammatory cytokines. However, the expression of Toll-like receptors, MYD88, RNF36, IRF3, and TBK1 and inhibitors of the NF-kappaB gene was not altered. A. phagocytophilum infection also altered the apoptotic program of NB4 cells and resulted in increased transcription of antiapoptotic genes (MCL1 and BFL1). The transcription and translation of iron-metabolism genes (light polypeptide ferritin chain, transferrin, and the transferrin receptor) were significantly altered, suggesting a possible link between A. phagocytophilum infection and iron metabolism. Our study clearly demonstrates multifactorial effects of A. phagocytophilum infection on NB4 promyelocytic leukemic cell machinery.
嗜吞噬细胞无形体是一种革兰氏阴性专性细胞内细菌，寄生于嗜中性粒细胞内。我们使用高密度寡核苷酸芯片、二维差异凝胶电泳和液相色谱-质谱联用技术，评估了嗜吞噬细胞无形体感染对NB4早幼粒细胞白血病细胞的影响。我们的Affymetrix数据显示，嗜吞噬细胞无形体改变了转录因子、细胞黏附分子、信号转导基因和促炎细胞因子的表达。然而，Toll样受体、MYD88、RNF36、IRF3和TBK1以及NF-κB基因抑制剂的表达未发生改变。嗜吞噬细胞无形体感染还改变了NB4细胞的凋亡程序，并导致抗凋亡基因（MCL1和BFL1）的转录增加。铁代谢基因（轻链铁蛋白多肽链、转铁蛋白和转铁蛋白受体）的转录和翻译发生了显著改变，提示嗜吞噬细胞无形体感染与铁代谢之间可能存在联系。我们的研究清楚地证明了嗜吞噬细胞无形体感染对NB4早幼粒细胞白血病细胞机制的多因素影响。
