G. Piedimonte et al., Respiratory syncytial virus upregulates expression of the substance P receptor in rat lungs, AM J P-LUNG, 277(4), 1999, pp. L831-L840
Citations number
47
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Respiratory syncytial virus (RSV) is a major respiratory pathogen in infant
s. The first goal of this study was to determine whether the infection foll
owing endotracheal inoculation of RSV in Fischer 344 rats results in increa
sed inflammatory responses to substance P (SP) either released by capsaicin
from sensory nerves or injected into the circulation. Five days after inoc
ulation, the extravasation of Evans blue-labeled albumin after capsaicin or
SP was significantly greater in RSV-infected airways than in pathogen-free
controls. The peptide-degrading activity of the regulatory enzyme neutral
endopeptidase was unaffected by RSV. However, SP(NK1) receptor mRNA levels
increased fivefold in RSV-infected lungs, and the density of SP binding sit
es in the bronchial mucosa increased threefold. These data suggest that RSV
makes the airways abnormally susceptible to the proinflammatory effects of
SP by upregulating SP(NK1) receptor gene expression, thereby increasing th
e density of these receptors on target cells. This effect may contribute to
the inflammatory reaction to the virus and could be a target for the thera
py of RSV disease and its sequelae.