Gene expression profiling of avian macrophage activation
Gene expression profiling of avian macrophage activation
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DOI：
10.1016/j.vetimm.2005.02.013
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发表时间：
2005-05-15
影响因子：
1.8
通讯作者：
Keeler, CL
中科院分区：
文献类型：
--
作者：
Bliss, TW;Dohms, JE;Keeler, CL
通过吞噬作用，巨噬细胞负责清除和破坏细胞内和细胞外病原体。当受到刺激时，巨噬细胞经历活化过程，包括大小和运动性的增加，增强的吞噬、杀菌和杀肿瘤活性，以及几种细胞表面标志物的上调。一种充分表征的哺乳动物巨噬细胞活化方法涉及Toll样受体（TLR）途径。TLR是作为微生物组分的直接受体起作用的表面分子。配体与TLR的结合导致转录因子的活化，所述转录因子调节参与微生物杀伤、细胞凋亡和抗原识别的基因，以及促炎和抗炎细胞因子和趋化因子。我们构建了一个包含4906个单元（14，718个点）的禽类巨噬细胞特异性cDNA微阵列（AMM）。AMM包含哺乳动物TLR途径中鉴定的约44个基因中的16个。该阵列用于检查禽类巨噬细胞对革兰氏阴性细菌及其细胞壁组分的转录应答，并评估禽类TLR途径对该应答的贡献。在AMM上的元件中，981个（20%）在大肠杆菌的吞噬过程中表现出显著的表达变化（大于两倍，p < 0.01），243个（5%）在暴露于脂多糖（LPS）期间表现出显著的表达变化。观察到一组独特的重叠元件（154）在吞噬作用和LPS刺激的表达中表现出显著变化，代表一组核心应答元件。在这些元素中，63%通常被诱导，而32%通常被抑制。发现LPS和细菌均诱导NF κ β和TLR途径的几种终产物。(c)2005 Elsevier B.V.保留所有权利。
Through the process of phagocytosis, the macrophage is responsible for the clearance and destruction of both intracellular and extracellular pathogens. When stimulated, macrophages undergo a process of activation involving an increase in size and motility, enhanced phagocytic, bactericidal, and tumoricidal activity, and up-regulation of several cell-surface markers. One well characterized method of mammalian macrophage activation involves the Toll-like receptor (TLR) pathway. TLRs are surface molecules that function as direct receptors for microbial components. Binding of ligand to TLRs results in activation of transcription factors that regulate genes involved in microbial killing, apoptosis, and antigen recognition, as well as pro- and anti-inflammatory cytokines and chemokines. We have constructed a 4906-element (14,718 spot) avian macrophage-specific cDNA microarray (AMM). The AMM contains 16 of the approximately 44 genes identified within the mammalian TLR pathway. This array was used to examine the transcriptional response of avian macrophages to Gram-negative bacteria and their cell wall components and to evaluate the contribution of the avian TLR pathway to that response. Of the elements on the AMM, 981 (20%) exhibited significant (greater than two-fold, p < 0.01) changes in expression during phagocytosis of Escherichia coli and 243 (5%) exhibited significant expression changes during exposure to lipopolysaccharide (LPS). A unique set of overlapping elements (154), were observed to exhibit significant changes in expression for both phagocytosis and LPS stimulation, representing a set of core response elements. Of these elements, 63% were commonly induced, while 32% were commonly repressed. Both LPS and bacteria were found to induce NF kappa beta and several end products of the TLR pathway. (c) 2005 Elsevier B.V. All rights reserved.