Ew. Uhl et al., PARAINFLUENZA VIRUS-INDUCED PERSISTENCE OF AIRWAY INFLAMMATION, FIBROSIS, AND DYSFUNCTION ASSOCIATED WITH TGF-BETA(1), EXPRESSION IN BROWN-NORWAY RATS, American journal of respiratory and critical care medicine, 154(6), 1996, pp. 1834-1842
Citations number
34
Categorie Soggetti
Emergency Medicine & Critical Care","Respiratory System
Parainfluenza type 1 (Sendai) virus infection in young rats induces ai
rway grow abnormalities associated with persistent pulmonary dysfuncti
on and hyperresponsiveness. The objectives of this study were to compa
re virus-susceptible brown Norway (BN) rats and virus-resistant F344 r
ats and to determine which of several virus-induced structural abnorma
lities, including bonchiolar hypoplasia, alveolar dysplasia, bronchiol
ar mural fibrosis, and increases in bronchiolar mast cells, were assoc
iated with virus-induced increases in pulmonary resistance and hyperre
sponsiveness to methacholine. We also determined whether bronchiolar m
ural thickening and fibrosis may be caused by increased bronchiolar ex
pression of cytokines such as TGF-beta 1 into airways. BN rats infecte
d with virus developed increases in respiratory resistance and hyperre
sponsiveness that persisted for 28 to 65 d after inoculation. Function
al abnormalities were most strongly associated with bronchiolar mural
thickening and fibrosis as well as with recruitment of inflammatory ce
lls, including macrophages, mast cells, lymphocytes, and eosinophils,
into the bronchiolar wall. F344 rats were resistant to significant vir
us-induced alterations in bronchiolar airway wall thickness and mast c
ell increases as well as to pulmonary function abnormalities. BN rats
had increase pulmonary mRNA levels of TGF-beta 1 at 10 and 14 d after
viral inoculation as compared with F344 rats. BN rats also had greater
numbers of bronchiolar macrophages expressing TGF-beta(1) protein tha
t were localized in bronchiolar walls al 10, 1 a, and 30 d after inocu
lation. We conclude that recruitment-and persistance of airway inflamm
atory cells and airway wall fibrosis may be important alterations indu
ced by viral sower respiratory disease during early life that can lead
to longterm airway dysfunction and hyperresponsiveness. Virus-induced
airway fibrosis may be mediated in part by increased TGF-beta(1) gene
expression by bronchiolar macrophages in genetically susceptible indi
viduals.