Klemens James Joseph, Thompson Kenneth, Langerman Alexander, Naclerio Robert M
Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL 60637-1035, USA.
Laryngoscope. 2006 Jul;116(7):1236-40. doi: 10.1097/01.mlg.0000224526.43698.52.
To develop a murine model of viral rhinosinusitis.
Randomized, controlled, animal model.
Mice were intranasally inoculated with Sendai virus (SeV) or ultraviolet (UV)-inactivated virus. On days 3 and 10 postinfection, nasal lavage fluid was obtained for viral culture. On days 4, 10, and 38 postinfection, sinus mucosa was harvested and analyzed by flow cytometry for CD3-, CD4-, CD8-, CD25-, CD11b-, CCR3-, and GR1-positive cells. Nasal hyperresponsiveness to histamine challenge was measured on days 8 and 36 postinoculation.
On day 3, viral cultures were positive from all SeV-inoculated mice but from none of the UV-inactivated mice (P<or=.0039). There was no growth of virus from either group on day 10. On day 4, flow cytometry on SeV-infected sinus cells showed a significant increase in macrophages (P<or=.03) and neutrophils (P<or=.02) compared with controls. This inflammation resolved by day 10. On day 38, mice inoculated with SeV had significantly more CD8+ (P<or=.044) and CD4+CD25+ (P<or=.017) cells than did controls. On day 8, there was a significant increase in both sneezing (P<or=.002) and nasal rubbing (P<or=.002) in the SeV-infected group to histamine challenge compared with controls. This difference continued to day 36.
Inoculation with SeV results in an acute infection that resolves spontaneously within 10 days. Infected mice develop a significant increase in T-suppressor and T-regulatory cells after resolution of the acute infection, which persists for at least 38 days. The persistence of these T cells is associated with hyperresponsiveness to histamine. This mouse model has some parallels to chronic rhinosinusitis after a viral infection in humans and should allow us to clarify the pathophysiology of this disease.
建立病毒性鼻-鼻窦炎的小鼠模型。
随机对照动物模型。
通过鼻腔接种仙台病毒（SeV）或紫外线（UV）灭活病毒。在感染后第3天和第10天，采集鼻腔灌洗液进行病毒培养。在感染后第4天、第10天和第38天，采集鼻窦黏膜，通过流式细胞术分析CD3、CD4、CD8、CD25、CD11b、CCR3和GR1阳性细胞。在接种后第8天和第36天测量鼻腔对组胺激发的高反应性。
在第3天，所有接种SeV的小鼠病毒培养呈阳性，而接种UV灭活病毒的小鼠均为阴性（P≤0.0039）。在第10天，两组均无病毒生长。在第4天，与对照组相比，SeV感染的鼻窦细胞流式细胞术显示巨噬细胞（P≤0.03）和中性粒细胞（P≤0.02）显著增加。这种炎症在第10天消退。在第38天，接种SeV的小鼠CD8 +（P≤0.044）和CD4 + CD25 +（P≤0.017）细胞明显多于对照组。在第8天，与对照组相比，SeV感染组对组胺激发的打喷嚏（P≤0.002）和擦鼻（P≤0.002）均显著增加。这种差异持续到第36天。
接种SeV导致急性感染，10天内可自发消退。急性感染消退后，感染小鼠的T抑制细胞和T调节细胞显著增加，持续至少38天。这些T细胞的持续存在与对组胺的高反应性有关。该小鼠模型与人类病毒感染后的慢性鼻-鼻窦炎有一些相似之处，应有助于我们阐明该疾病的病理生理学。
