ABSTRACT
The effect of ovalbumin (Ova) sensitization on pulmonary C-fiber sensitivity was investigated. Brown-Norway rats were sensitized by intraperitoneal injection of Ova followed by aerosolized Ova three times per week for 3 wk. Control rats received the vehicle. At the end of the third week, single-unit fiber activities (FA) of pulmonary C fibers were recorded in anesthetized, artificially ventilated rats. Our results showed the following: 1) Ova sensitization induced airway inflammation (infiltration of eosinophils and neutrophils) and airway hyperresponsiveness in rats; 2) baseline FA in sensitized rats was significantly higher than that in control ones; 3) similarly, the pulmonary C-fiber response to right atrial injection of capsaicin was markedly higher in sensitized rats, which were significantly amplified after the acute Ova inhalation challenge; and 4) similar patterns, but smaller magnitudes of the differences in C-fiber responses to adenosine and lung inflation, were also found between sensitized and control rats. In conclusion, Ova sensitization elevated the baseline FA and excitability of pulmonary C fibers, and the hypersensitivity was further potentiated after the acute Ova inhalation challenge in sensitized rats. Chronic allergic inflammatory reactions in the airway probably contributed to the sensitizing effect on these lung afferents.
Subject(s)
Hypersensitivity/immunology , Lung/innervation , Nerve Fibers, Unmyelinated/physiology , Ovalbumin/immunology , Administration, Inhalation , Aerosols , Allergens/administration & dosage , Allergens/immunology , Animals , Blood Pressure/drug effects , Blood Pressure/physiology , Bronchial Hyperreactivity/physiopathology , Bronchoconstrictor Agents/pharmacology , Dose-Response Relationship, Drug , Heart Rate/drug effects , Heart Rate/physiology , Inflammation/pathology , Lung/physiology , Male , Methacholine Chloride/pharmacology , Neurons, Afferent/drug effects , Neurons, Afferent/physiology , Ovalbumin/administration & dosage , Rats , Rats, Inbred BNABSTRACT
It has been shown that airway exposure to eosinophil-derived cationic proteins stimulated vagal pulmonary C fibers and markedly potentiated their responses to lung inflation in anesthetized rats (Lee LY, Gu Q, Gleich GJ, J Appl Physiol 91: 1318-1326, 2001). However, whether the effects resulted from a direct action of these proteins on the sensory nerves was not known. The present study was therefore carried out to determine the effects of these proteins on isolated rat vagal pulmonary sensory neurons. Our results obtained from perforated whole cell patch-clamp recordings showed that pretreatment with eosinophil major basic protein (MBP; 2 microM, 60 s) significantly increased the capsaicin-evoked inward current in these neurons; this effect peaked approximately 10 min after MBP and lasted for >60 min; in current-clamp mode, MBP substantially increased the number of action potentials evoked by both capsaicin and electrical stimulation. Pretreatment with MBP did not significantly alter the input resistance of these sensory neurons. In addition, the sensitizing effect of MBP was completely abolished when its cationic charge was neutralized by mixing with a polyanion, such as low-molecular-weight heparin or poly-L-glutamic or poly-L-aspartic acid, before its delivery to the neurons. Moreover, a similar sensitizing effect was also generated by other eosinophil granule-derived proteins (e.g., eosinophil peroxidase). These results demonstrate a direct, charge-dependent, and long-lasting sensitizing effect of cationic proteins on pulmonary sensory neurons, which may contribute to the airway hyperresponsiveness associated with airway infiltration of eosinophils under pathophysiological conditions.
