Am. J. Respir. Cell Mol. Biol., Volume 24, Number 2, February, 2001 101-107

Exaggerated Neurogenic Inflammation and Substance P Receptor Upregulation in RSV-Infected Weanling Rats

Katherine A. King, Chengping Hu, Maria M. Rodriguez, Rita Romaguera, Xiaobo Jiang, and Giovanni Piedimonte

Departments of Pediatrics, Medicine, Molecular and Cellular Pharmacology, and Pathology, University of Miami School of Medicine, Miami, Florida

Respiratory syncytial virus (RSV) infection in adult rats causes exaggerated inflammation after sensory nerve stimulation in the extrapulmonary, but not in the intrapulmonary airways. The goal of this study was to analyze neurogenic inflammation in weanling F-344 rats infected with RSV 18 ± 2 d after birth. Five days after RSV inoculation, the extravasation of Evans blue-labeled albumin after nerve stimulation was significantly greater in the intrapulmonary airways of RSV-infected weanling rats than in pathogen-free control rats. In contrast, no difference was found in the extrapulmonary airways. The level of messenger RNA (mRNA) encoding the substance P (SP) receptor (neurokinin 1 [NK1]) increased fourfold in RSV-infected lungs, whereas mRNA encoding the VIPR1 receptor for the antiinflammatory vasoactive intestinal peptide (VIP) increased to a much lesser degree. mRNAs encoding the other neurokinin (NK2) and VIP (VIPR2) receptors were not affected by the virus. Selective inhibition of the NK1 receptor abolished neurogenic inflammation in RSV-infected intrapulmonary airways. Also, neurogenic inflammation and NK1 receptor upregulation in infected lungs were inhibited by prophylaxis 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.

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