Sendai virus infection potentiates neurogenic inflammation in the rat trachea

Abstract

The goal of this study was to determine whether Sendai (parainfluenza type I) virus infection potentiates neurogenic inflammatory responses in the trachea. Pathogen-free F344 male rats were inoculated into each nostril with Sendai virus or with sterile culture medium. Six days after the inoculation, a threshold dose of capsaicin (75 micrograms/kg) or the vehicle used to dissolve the capsaicin was injected intravenously, and Monastral blue pigment was injected to measure the increase in vascular permeability produced by the capsaicin or vehicle (n = 6 per group). Five minutes later the tracheae were fixed by vascular perfusion, removed, and treated with a histochemical reaction for myeloperoxidase to stain the neutrophils in the mucosa, and the magnitude of the Monastral blue extravasation was determined both by stereological point counting and by microspectrophotometry. Capsaicin produced a larger number of Monastral blue-labeled blood vessels in the rats infected with Sendai virus than in the uninfected rats or in any of the rats that received only the vehicle. In addition, capsaicin further increased the already large number of neutrophils in the tracheal mucosa of the infected rats. However, in the dose used, it had no detectable effect on neutrophils in the uninfected rats. We conclude that Sendai virus infection causes neutrophil chemotaxis but does not increase vascular permeability in the trachea; it does, however, make the trachea abnormally susceptible to neurogenic inflammation, as manifested by an unusually large increase in vascular permeability and an exaggerated influx of neutrophils in response to sensory nerve stimulation by capsaicin.

Mycoplasma pulmonis infections cause long-lasting potentiation of neurogenic inflammation in the respiratory tract of the rat.

“…This question needed to be addressed because viral infections can potentiate neurogenic inflammation (19) and can make mycoplasmal infections worse (21,22). These complicating factors were avoided, first, by using rats that had been raised under barrier conditions and were known to be pathogen-free at the outset and, second, by housing the rats under barrier conditions during the 4-wk experiment.…”

“…First, the potentiation of neurogenic inflammation by M. pulmonis infections was present 4 wk after inoculation and probably was permanent, as these infections persist throughout life. By comparison, the potentiation of neurogenic inflammation by Sendai virus infections has only been detected 6 d after inoculation (19). In adult rats, Sendai virus infections peak within a week, and the resulting pathological changes in the trachea and bronchi resolve in 10-17 d (40,41).…”

“…Of potential clinical relevance, the magnitude ofthe neurogenic inflammatory response is altered by viral respiratory tract infections (17)(18)(19). For example, experimentally induced parainfluenza virus infections augment the contraction of airway smooth muscle induced by substance P and capsaicin, a sensory nerve stimulant (17,18).…”

“…For example, experimentally induced parainfluenza virus infections augment the contraction of airway smooth muscle induced by substance P and capsaicin, a sensory nerve stimulant (17,18). The infections also potentiate the increase in vascular permeability evoked by capsaicin (19). These changes coincide with the peak of the viral infections, some 4-6 d after their onset. Neurogenic inflammation is also potentiated by naturally occurring respiratory tract infections due to a combination of organisms, including parainfluenza type I (Sendai) virus, coronavirus (sialodacryoadenitis virus/rat coronavirus), and Mycoplasma pulmonis (12,20).…”

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

“…Point counts were made by superimposing a computer-generated grid of 51 points spaced at 25-mm intervals on the televised image of the specimens magnified 380 times with a stereomicroscope (9,17). Monastral blue area density was expressed as the average ofvalues measured in 20 regions (each measuring 0.3 mm2 in area) located between cartilaginous rings, from ring 5 to ring 25, on the right side of each tracheal whole mount.…”