Degranulation of Mast Cells in the Trachea and Bronchi of the Rat following Stimulation of the Vagus Nerve

Abstract. In the trachea and bronchi of the atropinized rat, the proportion of degranulating mast cells (de­fined as having one or more granules outside the body of the cell in a lO-llm thick section) was increased from 35-40% to 48-55% following electrical stimulation of one or both vagus nerves for 3 min. The increase occurred bilaterally, though it was greater on the stimulated side. The degranulation of mast cells was prevented by transection of the nerve rostral to the nodose ganglion 8-10 days before stimulation. Pre-treatment of rats with capsaicin also prevented the degranulation of mast cells that otherwise would have followed stimulation of the vagus nerve. These observations indicate that tracheo-bronchial mast cells discharge their granules in response to the activity of capsaicin-sensitive axons of neurons whose cell bodies are rostral to the nodose ganglion. These are probably substance P-containing polymodal nociceptive neurons of the jugular ganglion. If similar neurons exist in man, axon reflexes in their intrabronchial branches would be expected to stimulate the release of mast cell-derived agents that cause bronchoconstriction in asthma. An axon reflex causes the flare of arteriolar vaso­dilatation at and around the site of a minor cutaneous injury or a. noxious chemical stimulus. There is also increased vascular permeability, a condition known as neurogenic inflammation, throughout the affected region. The axons that mediate these responses are unmyelinated nociceptive fibres. Their vascular ac­tions are due to substance P, which is released when impulses travel antidromically (centrifugally) in the axons, in the direction opposite to that taken by peripherally arising sensory signals. Neurogenic in­flammation in skin is prevented by prior treatment with capsaicin, a compound that stimulates and then intoxicates substance P-containing sensory axons [1,2]. Impulses travelling antidromically in the sensory fibres of a cutaneous nerve also cause degranulation of dermal mast cells [3]. Depletion of an animal's mast cells by compound 48/80 reduces the severity of axon reflex vasodilatation [4] and of neurogenic inflamma­tion due to topical chemical irritation or to electrical stimulation of a cutaneous nerve [5, 6]. Thus, the ac­tion of substance P released from nociceptive axons in skin is mediated partly by a direct action of the peptide on blood vessels and partly by other vasoac­tive agents, which are secreted by mast cells [7-9]. Application or injection of substance P evokes mast cell degranulation [10, 11] and inflammation in several organs other than the skin, including the mouth, pharynx, trachea, oesophagus and urinary bladder [12], and it is possible that axon reflexes are involved in the responses of these tissues to injury or irritation. In the mucosa of the small intestine, nerve fibres are in contact with mast cells [13, 14], and may modulate inflammatory reactions due to nematode inC estation [15], Stimulation of the vagus nerve, which provides sensory and autonomic innervation to the respiratory tract, causes vasodilatation, bronchoconstriction, and increased vascular and epithelial permeability [16]. Some of these events are prevented by prior treatment with capsaicin [17], which is presumed to act by de­pleting the substance P-containing sensory fibres of the mucosa. In the trachea and bronchi, mast cells occur in con­nective tissue beneath the luminal surface and among nearby smooth muscle fibres [18-20], and their de­granulation is associated with bronchoconstriction