A MOUSE MODEL FOR INVESTIGATING THE MOLECULAR PATHOGENESIS OF ADENOVIRUS PNEUMONIA
A MOUSE MODEL FOR INVESTIGATING THE MOLECULAR PATHOGENESIS OF ADENOVIRUS PNEUMONIA
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DOI：
10.1073/pnas.88.5.1651
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发表时间：
1991-03-01
影响因子：
11.1
通讯作者：
PRINCE, GA
中科院分区：
文献类型：
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作者：
GINSBERG, HS;MOLDAWER, LL;PRINCE, GA
鼻内接种 5 型腺病毒 (Ad5) 会在小鼠体内产生肺炎，尽管该病毒不复制。然而，要诱发肺炎，需要大的病毒感染剂量，即 10(10) 个噬菌斑形成单位。研究了四种近交小鼠品系（C57BL/6N、C57BL/10ScN、CBA/N 和 C3H/N）：尽管最大的浸润发生在 C57BL/6N 小鼠中，但所有小鼠均表现出相似的炎症反应。 Ad5感染的病理反应类似于之前在棉鼠中描述的病理反应：它由重叠的早期和晚期阶段组成，并且浸润主要包含淋巴细胞和单核细胞/巨噬细胞，以及分散的多形核白细胞。突出的早期阶段和多形核白细胞的存在表明细胞因子的诱导可能在这种肺炎的发病机制中发挥重要作用。检测显示，受感染小鼠肺部出现肿瘤坏死因子-α (TNF-α)、白细胞介素 1 (IL-1) 和 IL-6，并伴有早期浸润的发展。外周血中仅发现IL-6。 IL-6在感染后6-24小时达到最大滴度，而TNF-α和IL-1在感染后2-3天达到最大水平。在受感染的肺部中证实了每种细胞因子的特异性 RNA。为了测试细胞毒性 T 细胞反应导致第二阶段（主要包括淋巴细胞血管周围和支气管周围浸润）的假设，使用 Ad5 感染 C57BL/10ScN Nu/Nu 和亲本小鼠。裸鼠表现出正常的早期反应，但基本上没有发生支气管周围浸润，仅发生极少量的血管周围浸润。
Intranasal inoculation of type 5 adenovirus (Ad5) produced pneumonia in mice even though the virus did not replicate. To induce the pneumonia, however, a large viral infectious dose was required - i.e., 10(10) plaque-forming units. Four strains of inbred mouse were studied (C57BL/6N, C57BL/10ScN, CBA/N, and C3H/N): all showed similar inflammatory responses, although the greatest infiltration occurred in the C57BL/6N mice. The pathological response to Ad5 infection resembled that previously described in cotton rats: it consisted of overlapping early and late phases, and the infiltration contained primarily lymphocytes and monocytes/macrophages with a scattering of polymorphonuclear leukocytes. The prominent early phase and the presence of polymorphonuclear leukocytes suggested that induction of cytokines may play an important role in the pathogenesis of this pneumonia. Assays showed the appearance of tumor necrosis factor-alpha (TNF-alpha), interleukin 1(IL-1), and IL-6 in the infected mouse lungs concomitant with the developing early-phase infiltration. Only IL-6 was found in the peripheral blood. IL-6 reached maximum titers 6-24 hr after infection, whereas maximum levels of TNF-alpha and IL-1 were attained 2-3 days after infection. Specific RNAs for each of these cytokines were demonstrated in the infected lungs. To test the hypothesis that a cytotoxic T-cell response was responsible for the second phase, which primarily consisted of a perivascular and peribronchial infiltration of lymphocytes, Ad5 was used to infect C57BL/10ScN Nu/Nu and parent mice. The nude mice showed a normal early-phase response, but essentially no peribronchial and only minimal perivascular infiltrations occurred.