Castleman W L, Brundage-Anguish L J, Kreitzer L, Neuenschwander S B
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706.
Am J Pathol. 1987 Nov;129(2):277-86.
The objective of this research was to identify potential mechanisms that might account for the greater susceptibility of neonatal rats (5 days old) as compared with weanling rats (25 days old) to viral-induced lung injury. Sites of viral replication, the sequential development of bronchiolitis and pneumonia, and systemic humoral immune responses were compared between neonatal and weanling rats from 2 to 17 days after being inoculated intranasally with parainfluenza Type 1 (Sendai) virus. In both neonatal and weanling rats, viral antigen was demonstrated by immunoperoxidase technique and viral nucleocapsids, and budding virions were demonstrated by transmission electron microscopy in bronchiolar ciliated and nonciliated epithelial cells as early as 2 days after inoculation. Similar evidence of viral replication was also demonstrated in both ages of rats in alveolar Type I and Type II epithelial cells and in macrophages. Neither virus nor viral antigens was identified in endothelial cells or interstitial cells of interalveolar septa. Bronchiolitis was induced as early as 2 days after inoculation in both ages of rats and was characterized by necrosis, erosion, and hyperplasia of epithelial cells. Multifocal to locally extensive interstitial pneumonia centered on bronchioles, was characterized by alveolar epithelial cell damage and by infiltration of neutrophils, macrophages, and lymphocytes in alveolar septa and spaces and was observed as early as 2 days after inoculation in both age groups of rats. Interstitial pneumonia of maximal severity occurred in weanling rats at 5 days after inoculation, whereas maximal pneumonia of comparable severity occurred in neonatal rats at 8 days after inoculation. Epithelial repair and resolution of bronchiolitis and pneumonia were largely complete in both ages of rats by 17 days after inoculation. Virus was recovered from lung homogenates of neonatal and weanling rats as early as 2 days after inoculation. In weanling rats, infective virus could not be recovered from lung beyond 6 days after inoculation, whereas in neonatal rats virus could be recovered from lung as late as 10 days after inoculation. Viral persistence in neonatal rats was associated with a delayed onset of serum antibody to the virus, compared with weanling rats. The results indicate that the cellular sites of viral replication and the pattern of inflammatory reactions are closely comparable between neonatal and weanling rats inoculated with Sendai virus.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究的目的是确定与断奶大鼠（25日龄）相比，新生大鼠（5日龄）对病毒诱导的肺损伤更易感的潜在机制。在新生大鼠和断奶大鼠经鼻接种1型副流感病毒（仙台病毒）后2至17天，比较病毒复制位点、细支气管炎和肺炎的序贯发展以及全身体液免疫反应。在新生大鼠和断奶大鼠中，早在接种后2天，通过免疫过氧化物酶技术即可在细支气管纤毛和非纤毛上皮细胞中证实病毒抗原，通过透射电子显微镜可证实病毒核衣壳和出芽的病毒粒子。在肺泡I型和II型上皮细胞以及巨噬细胞中，也在这两个年龄段的大鼠中发现了类似的病毒复制证据。在肺泡间隔的内皮细胞或间质细胞中未发现病毒或病毒抗原。早在接种后2天，在这两个年龄段的大鼠中均诱导出了细支气管炎，其特征为上皮细胞坏死、糜烂和增生。以细支气管为中心的多灶性至局部广泛的间质性肺炎，其特征为肺泡上皮细胞损伤以及中性粒细胞、巨噬细胞和淋巴细胞浸润肺泡间隔和肺泡腔，在这两个年龄段的大鼠中，早在接种后2天即可观察到。接种后5天，断奶大鼠出现了最严重的间质性肺炎，而接种后8天，新生大鼠出现了具有相当严重程度的最严重肺炎。接种后17天，在这两个年龄段的大鼠中，上皮修复以及细支气管炎和肺炎的消退基本完成。早在接种后2天，即可从新生大鼠和断奶大鼠的肺匀浆中分离出病毒。在断奶大鼠中，接种后6天以上无法从肺中分离出感染性病毒，而在新生大鼠中，接种后10天仍可从肺中分离出病毒。与断奶大鼠相比，新生大鼠中病毒的持续存在与针对该病毒的血清抗体延迟出现有关。结果表明，接种仙台病毒的新生大鼠和断奶大鼠之间，病毒复制的细胞位点和炎症反应模式密切相似。（摘要截选至400字）
