Grunstein M M, Hakonarson H, Whelan R, Yu Z, Grunstein J S, Chuang S
Division of Pulmonary Medicine, Joseph Stokes, Jr, Research Institute, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
J Allergy Clin Immunol. 2001 Dec;108(6):997-1004. doi: 10.1067/mai.2001.120276.
Rhinovirus (RV), the principal pathogen responsible for the common cold, is importantly implicated in triggering attacks of asthma secondary to changes in airway responsiveness.
Because the airway histopathologic features of RV infection are relatively modest, we tested the hypothesis that RV can directly elicit proasthmatic-like changes in airway smooth muscle (ASM) responsiveness independently of actual viral infection and its associated cytopathic effects.
Isolated ASM tissues and cultured ASM cells were inoculated with either infectious or noninfectious (UV-irradiated) RV16 and RV2, the latter serotypes belonging to the "major" and "minor" groups of RV subtypes, respectively. ASM constrictor and relaxant responsiveness, G(i) protein expression, and proinflammatory cytokine release were subsequently compared under the different treatment conditions.
In contrast to RV2, which had no effect, RV16 inoculation elicited enhanced ASM contractility and impaired relaxation to cholinergic and beta-adrenergic agonists, respectively, in association with increased ASM membrane G(i) protein expression and induced release of the proinflammatory cytokines IL-5 and IL-1beta. These proasthmatic-like effects were also observed in ASM exposed to UV-irradiated RV16, wherein viral replication was completely inhibited. In contrast, pretreatment of ASM with a neutralizing antibody directed against ICAM-1, the host receptor for the "major" group of RVs, completely abrogated the proasthmatic effects of RV16.
The results demonstrate that (1) RV16 elicits proasthmatic changes in ASM responsiveness that can occur independently of actual viral infection of the ASM and (2) the effects of RV16 are attributed solely to binding of the virus to its host receptor (ICAM-1) on the ASM cell surface. Collectively, these findings support the notion that RV-induced exacerbation of wheezing in asthmatic individuals can occur even in the absence of any cytopathology associated with viral infection.
鼻病毒（RV）是引起普通感冒的主要病原体，在引发气道反应性改变继发的哮喘发作中具有重要作用。
由于RV感染的气道组织病理学特征相对不明显，我们检验了以下假设：RV可独立于实际病毒感染及其相关细胞病变效应，直接引发气道平滑肌（ASM）反应性出现类哮喘样改变。
分别用感染性或非感染性（紫外线照射）RV16和RV2接种分离的ASM组织和培养的ASM细胞，后两种血清型分别属于RV亚型的“主要”和“次要”组。随后比较不同处理条件下ASM收缩剂和松弛剂反应性、G(i)蛋白表达及促炎细胞因子释放情况。
与无作用的RV2相反，接种RV16可分别增强ASM收缩性并损害其对胆碱能和β-肾上腺素能激动剂的松弛反应，同时伴有ASM膜G(i)蛋白表达增加及促炎细胞因子IL-5和IL-1β的诱导性释放。在暴露于紫外线照射的RV16的ASM中也观察到这些类哮喘样效应，其中病毒复制被完全抑制。相反，用针对RV“主要”组的宿主受体ICAM-1的中和抗体预处理ASM，可完全消除RV16的哮喘样效应。
结果表明，（1）RV16可引发ASM反应性的类哮喘样改变，且这种改变可独立于ASM的实际病毒感染而发生；（2）RV16的效应完全归因于病毒与其在ASM细胞表面的宿主受体（ICAM-1）结合。总体而言，这些发现支持以下观点：即使在没有任何与病毒感染相关的细胞病理学情况下，RV也可导致哮喘患者喘息加重。
