TY - JOUR
T1 - Sensory denervation by neonatal capsaicin treatment exacerbates Mycoplasma pulmonis infection in rat airways
AU - Bowden, Jeffrey J.
AU - Baluk, Peter
AU - Lefevre, Peter M.
AU - Schoeb, Trenton R.
AU - Lindsey, J. Russell
AU - McDonald, Donald M.
PY - 1996/3/1
Y1 - 1996/3/1
N2 - Mycoplasma pulmonis infection in rats results in life-long disease, characterized by chronic inflammation of the airway mucosa with widespread accumulation of lymphoid tissue, mucous cell hyperplasia, and mucosal thickening. In addition, there is angiogenesis and increased sensitivity of mucosal blood vessels to substance P (SP), so tachykinins released from sensory nerve fibers cause an abnormally large amount of plasma leakage. We sought to learn whether the sensory nerves influence the severity of the chronic inflammatory response of M. pulmonis infection. Our strategy was to destroy the nerves by capsaicin pretreatment at birth, infect the rats with M. pulmonis at 8 wk of age, and then study the animals 6 wk later. We found that capsaicin pretreatment increased the severity of the infection, exaggerated the pathological changes in the tracheal mucosa, and increased the amount of SP-induced plasma leakage, as quantified with Monastral blue. The thickness of the tracheal mucosa in these infected rats was 80% greater than in their vehicle-pretreated counterparts and 200% greater than in the pathogen-free controls. The area density of Monastral blue-labeled blood vessels averaged 20% in the infected rats pretreated with capsaicin, which represented a 40-fold increase over the leakage in the pathogen-free group. By comparison, the amount of Monastral blue labeling was only 13% in rats pretreated with vehicle (P < 0.05), which was a 22-fold increase over the corresponding pathogen-free group. The number of SP-immunoreactive nerves fibers was reduced both by neonatal capsaicin and by infection (87 and 63% reductions, respectively); but when the two conditions were combined, their effects were not additive (79% reduction), perhaps because of nerve regrowth. We conclude that destruction of sensory nerves increases the severity of infection-induced chronic inflammation in the airway mucosa, with exaggerated mucosal thickening, angiogenesis, plasma leakage, and nerve remodeling.
AB - Mycoplasma pulmonis infection in rats results in life-long disease, characterized by chronic inflammation of the airway mucosa with widespread accumulation of lymphoid tissue, mucous cell hyperplasia, and mucosal thickening. In addition, there is angiogenesis and increased sensitivity of mucosal blood vessels to substance P (SP), so tachykinins released from sensory nerve fibers cause an abnormally large amount of plasma leakage. We sought to learn whether the sensory nerves influence the severity of the chronic inflammatory response of M. pulmonis infection. Our strategy was to destroy the nerves by capsaicin pretreatment at birth, infect the rats with M. pulmonis at 8 wk of age, and then study the animals 6 wk later. We found that capsaicin pretreatment increased the severity of the infection, exaggerated the pathological changes in the tracheal mucosa, and increased the amount of SP-induced plasma leakage, as quantified with Monastral blue. The thickness of the tracheal mucosa in these infected rats was 80% greater than in their vehicle-pretreated counterparts and 200% greater than in the pathogen-free controls. The area density of Monastral blue-labeled blood vessels averaged 20% in the infected rats pretreated with capsaicin, which represented a 40-fold increase over the leakage in the pathogen-free group. By comparison, the amount of Monastral blue labeling was only 13% in rats pretreated with vehicle (P < 0.05), which was a 22-fold increase over the corresponding pathogen-free group. The number of SP-immunoreactive nerves fibers was reduced both by neonatal capsaicin and by infection (87 and 63% reductions, respectively); but when the two conditions were combined, their effects were not additive (79% reduction), perhaps because of nerve regrowth. We conclude that destruction of sensory nerves increases the severity of infection-induced chronic inflammation in the airway mucosa, with exaggerated mucosal thickening, angiogenesis, plasma leakage, and nerve remodeling.
KW - angiogenesis
KW - chronic inflammation
KW - immunohistochemistry
KW - nerve regrowth
KW - PGP 9.5
KW - plasma leakage
KW - sensory nerves
KW - substance P
UR - http://www.scopus.com/inward/record.url?scp=0029866290&partnerID=8YFLogxK
U2 - 10.1152/ajplung.1996.270.3.L393
DO - 10.1152/ajplung.1996.270.3.L393
M3 - Article
C2 - 8638732
AN - SCOPUS:0029866290
SN - 1040-0605
VL - 270
SP - L393-L403
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 3
ER -