Ka. King et al., Exaggerated neurogenic inflammation and substance p receptor upregulation in RSV-infected weanling rats, AM J RESP C, 24(2), 2001, pp. 101-107
Citations number
34
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Respiratory syncytial virus (RSV) infection in adult rats causes exaggerate
d inflammation after sensory nerve stimulation in the extrapulmonary, but n
ot in the intrapulmonary airways. The goal of this study was to analyze neu
rogenic inflammation in weanling F-344 rats infected with RSV 18 +/- 2 d af
ter birth. Five days after RSV inoculation, the extravasation of Evens blue
-labeled albumin after nerve stimulation was significantly greater in the i
ntrapulmonary airways of RSV-infected weanling rats than in pathogen-free c
ontrol rats. In contrast, no difference was found in the extrapulmonary air
ways. The level of messenger RNA (mRNA) encoding the substance P (SP) recep
tor (neurokinin 1 [NK1]) increased fourfold in RSV-infected lungs, whereas
mRNA encoding the VIPR1 receptor for the antiinflammatory vasoactive intest
inal peptide (VIP) increased to a much lesser degree. mRNAs encoding the ot
her neurokinin (NK2) and VIP (VIPR2) receptors were not affected by the vir
us. Selective inhibition of the NK1 receptor abolished neurogenic inflammat
ion in RSV-infected intrapulmonary airways. Also, neurogenic inflammation a
nd NK1 receptor upregulation in infected lungs were inhibited by prophylaxi
s with a monoclonal antibody against RSV. These data suggest that RSV lower
respiratory tract infection makes the intrapulmonary airways of young rats
abnormally susceptible to the proinflammatory effects of SP by selectively
upregulating the expression of NK1 receptors.