Antigen-induced Lung Solute Clearance in Rats Is Dependent on Capsaicin-sensitive Nerves

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Abstract
Chemosensitive sensory nerves have an important effector role in the control of vascular permeability n rat airways after neurogenic inflammation. To investigate whether they also have a role in antigen-induced lung inflammation, we have studied the changes in lung solute clearance (LSC) in sensitized rats after aerosol challenge with allergen and the effect of prior capsaicin-induced denervation on these changes. Sprague-Dawley rats were immunized with egg albumin (EA), using aluminum hydroxide and Bordetella pertussis as adjuvants. After 11 days, the animals were challenged for 5 min with aerosolized EA, and the clearanc from the lungs of aerosolized 99mTc diethylenetriamine pentaacetic acid (99mTc-DTPA) over 7.5 min (LSC 7.5) was subsequently measured at various times after challenge as an index of epithelial permeability or integrity. Sensitized animals responded to the challenge with immediate respiratory symptoms and with an increased 99mTc-DTPA clearance rate that was detectable at 20 min (mean .+-. SE LSC 7.5; baseline, 6 .+-. 1%; 20 min, 17 .+-. 3%; p < 0.05), persisted at 4 h (14 .+-. 1%; p < 0.05), and returned to normal values after 24 h. Unsensitized rats exposed to EA and sensitized rats exposed to PBS or to bovine serum albumin did not show any change. Bronchoalveolar lavage failed to show significant changes of cell populations until 24 h, when an increased presence of lymphocytes, PMN, and eosinophils was observed. Sensitized rats that had been neonatally treated with capsaicin had reduced respiratory symptoms during EA challenge, and presented only a small increase in percent of 99mTc-DTPA cleared from the lungs compared with that in untreated littermates (baseline, 5 .+-. 1%; 20 min, 8 .+-. 1%; 4 h, 8 .+-. 1%; p < 0.05 versus control values at 20 min and at 4 h). There was no significant difference in the level of serum EA-specific IgE between control and capsaicin-treated rats. These data indicate that an early, relatively long-lasting, increase in lung clearance of 99mTc-DTPA is induced by allergen challenge in sensitized rats, and that capsaicin-sensitive nerves play an important effector role in this response.