Modulation of monocytic cell activity and virus susceptibility during differentiation into macrophages.

Modulation of monocytic cell activity and virus susceptibility during differentiation into macrophages.
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在分化为巨噬细胞过程中调节单核细胞活性和病毒敏感性。

DOI:
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发表时间:
1999
影响因子:
4.4
通讯作者:
K. McCullough
K. McCullough
中科院分区:
医学2区
文献类型:
--
作者:
Sameh Basta;S. Knoetig;M. Spagnuolo;G. Allan;K. McCullough

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先天性免疫应答的主要成分依赖于单核细胞和巨噬细胞,其病毒感染将对免疫防御造成特别的问题。因此,分析了单核细胞分化途径中的细胞调节及其与单核细胞病毒感染的关系。分化的特征在于CD 14、MHC Ag、单核细胞SWC 1标志物和p53的下调; SWC 9巨噬细胞标志物、推定的猪CD 80(用抗人CD 80 Ab检测)和酸性磷酸酶分泌的伴随上调也是特征性的。升高的吞噬和内吞活性以及内体/溶酶体酸化被确定为对巨噬细胞重要。与此相反,单核细胞具有较高的辅助活性。这是多因素的,同时需要1)高MHC Ag表达; 2)酯酶、过氧化物酶、髓过氧化物酶和5'核苷酸酶的酶活性优先于葡萄糖苷酶、半乳糖苷酶和葡萄糖醛酸糖苷酶; 3)自发IL-1产生的能力提高。只有所有参数的Ag特异性淋巴细胞的有效刺激是可能的。这些结果指向分化过程中的连续过程,包括将更多的辅助单核细胞与清道夫巨噬细胞在体外和体内联系起来的相互关联的特征。特别令人感兴趣的是这些特征如何与单核细胞病毒感染相关,以及特定病毒如何对分化中的巨噬细胞表现出明显的偏好。这些结果不仅加深了我们对猪免疫学的理解,而且为确定和表征单核细胞嗜性病毒-宿主细胞相互作用提供了证据和潜在的模型。
A major component of innate immune responses relies on monocytes and macrophages, virus infection of which will pose a particular problem for immunological defense. Consequently, the monocytic cell differentiation pathway was analyzed in terms of cellular modulations therein and their relation to monocytotropic virus infection. Differentiation was characterized by down-regulation of CD14, MHC Ags, the monocytic SWC1 marker, and p53; concomitant up-regulation of the SWC9 macrophage marker, a putative porcine CD80 (detected with anti-human CD80 Ab), and acid phosphatase secretion were also characteristic. Elevated phagocytic and endocytic activities as well as endosomal/lysosomal acidification were identified as being important to the macrophage. In contrast, monocytes possessed high accessory activity. This was multifactorial, concomitantly requiring 1) high MHC Ag expression; 2) enzyme activity of esterase, peroxidase, myeloperoxidase, and 5' nucleotidase in preference to glucosidase, galactosidase, and glucuronidase; and 3) elevated capacity for spontaneous IL-1 production. Only with all parameters was efficient stimulation of Ag-specific lymphocytes possible. These results point to a continuous process during differentiation, involving inter-related characteristics linking the more accessory monocyte to the scavenger macrophage, both in vitro and in vivo. Of particular interest was how these characteristics related to monocytotropic virus infection, and how a particular virus could show a clear preference for the differentiating macrophages. Such results not only further our understanding of porcine immunology, but also provide evidence and a potential model for the determination and characterization of monocytotropic virus-host cell interactions.
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