Histamine enhances vagal pulmonary C-fiber responses to capsaicin and lung inflation

Lee, Lu-Yuan; Morton, Robert F.

doi:10.1016/0034-5687(93)90070-q

Cited by 64 publications

(38 citation statements)

References 17 publications

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“…Indeed, eosinophil-derived cationic proteins such as MBP have been reported to release prostaglandins from epithelial cells (50) and histamine from mast cells (43,53) and basophils (45). These mediators are known to induce pronounced sensitizing effects on pulmonary C-fiber afferents, elevating their sensitivities to various chemical and mechanical stimulations (15,22,34). The importance of pulmonary C fibers in the regulation of airway functions in both physiological and pathophysiological conditions is well documented (8,35).…”

Section: Discussionmentioning

confidence: 99%

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Gu¹,

Wiggers²,

Gleich³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Gu Q, Wiggers ME, Gleich GJ, Lee L-Y. Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins. Am J Physiol Lung Cell Mol Physiol 294: L544-L552, 2008. First published January 4, 2008 doi:10.1152/ajplung.00271.2007.-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 M, 60 s) significantly increased the capsaicin-evoked inward current in these neurons; this effect peaked ϳ10 min after MBP and lasted for Ͼ60 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. major basic protein; eosinophil cationic protein; eosinophil peroxidase; airway inflammation; airway hypersensitivity ASTHMA IS CHARACTERIZED BY chronic airway inflammation associated with airway infiltration of various inflammatory cells, particularly the eosinophils (7). Activated eosinophils are known to secrete a number of cationic proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) (16). Previous studies have shown that intratracheal instillation of eosinophil-derived cationic proteins such as MBP induces bronchoconstriction and bronchial hyperresponsiveness in a number of animal species (9,17,21). Similar effects can also be induced by intratracheal administration of synthetic cationic proteins such as poly-Llysine (PLL) (10,24,46).Most of the sensory inputs arising from airways and lungs are conducted in vagus nerves and their branches. Cell bodies of these sensory nerves reside in two adjacent but distinct anatomic structures, the nodose and intracranial jugular ganglia. It is known that Ͼ75% of vagal bronchopulmonar...

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Section: Discussionmentioning

confidence: 99%

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Gu¹,

Wiggers²,

Gleich³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Histamine was delivered into the lungs by inhalation route to minimize its sustaining and diffusive systemic effects. The dose of histamine actually deposited in the lungs was not determined in their study, but it was estimated to be comparable to the higher levels of endogenously released histamine, judging from the degree of bronchoconstriction caused by the inhalation challenge (26). Their results show that this potentiating effect on Cfiber endings is not related to the bronchoconstrictive effect of histamine and is reversible 15-25 min later.…”

Section: Excitability Of Airway Afferents Modulated By Inflammatory Mmentioning

confidence: 93%

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Lee

Widdicombe

2001

Environ Health Perspect

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Among the three major types of sensory receptors innervating the airways and lungs, C-fiber endings and rapidly adapting pulmonary receptors (RARs or irritant receptors) are believed to be primarily responsible for eliciting the reflex responses in defending the lungs against inhaled irritants and toxins (1-3). The third type, slowly adapting pulmonary receptors (SARs or stretch receptors), plays an important role in regulating the respiratory volume-timing relationship (4), and is considered to be pure mechanoreceptor and relatively insensitive to chemical irritants. Several recent studies have attempted to uncover the mechanisms underlying the interaction between the pulmonary C fibers and RARs in the overall regulation of the defense reflex responses. Inhalation of cigarette smoke, a common inhaled irritant in human airways, has been shown to elicit irregular breathing pattern, cough reflex, and bronchoconstriction in a number of species including humans (5-9). Although it is believed that most of these responses are mediated through the activation of these two types of vagal afferents, the relative contributions of these two types of afferents to the emergence of these reflex responses are not known. In anesthetized animals (dogs, cats, or rats), spontaneous inhalation of one to two tidal breaths of cigarette smoke into the lungs via a tracheal cannula immediately elicited pulmonary chemoreflexes, characterized by apnea, bradycardia, and hypotension, known to be elicited by activation of pulmonary C fibers (1-3,6). After perineural capsaicin treatment of both cervical vagi to selectively block the conduction of capsaicin-sensitive C fibers, inhaled cigarette smoke no longer evoked any inhibitory effect on breathing (9). Conversely, an augmented inspiration, a reflex effect of activating RARs, was triggered within the first three breaths from the onset of cigarette smoke inhalation in > 85% of the rats studied (Figure 1). When the temperature of the vagus nerve was cooled progressively to 6-7 °C to block the conduction of myelinated afferents, as indicated by the ablation of the apneic response to lung inflation, the augmented breaths evoked by the cigarette smoke inhalation were also abolished (9). Both the apnea and augmented breath evoked by inhaled cigarette smoke were completely abolished by bilateral cervical vagotomy. Similarly, augmented breaths were also elicited when other chemical irritants such as sulfur dioxide (SO 2 ) (9), ammonia (NH 3 ) (9), acrolein (10), and wood smoke (11) were inhaled after the perineural capsaicin treatment of both vagi in anesthetized rats.It is interesting to note that augmented breaths were consistently elicited by inhaled irritants only after the conduction in bronchopulmonary C-fiber afferents are blocked by perineural capsaicin treatment of both vagi but were rarely seen when the same irritants were inhaled in the same animals with intact C fibers (9-11). These results suggest that both vagal bronchopulmonary C-fiber afferents and RARs are stimulated by these inhale...

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“…Several mediators released upon antigen challenge can influence the electrical properties of somal membranes of guinea-pig nodose ganglion neurons, including histamine, cysteinyl leukotrienes and prostacylin . Lee & Morton (1993), using single-unit recordings from the vagus nerve in dogs, demonstrated that intravenous histamine could increase the response of mechanosensitive afferent endings to lung inflation. The data in the present study, however, indicate that neither eicosanoids derived from cyclo-oxygenase or 5-lipoxygenase activity, nor histamine per se, are obligatory for the antigen-induced increase in mechanical sensitivity of airway Ad afferents to occur.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulation of afferent neurons in guinea‐pig isolated airway.

Riccio¹,

Myers²,

Undem³

1996

The Journal of Physiology

138

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1. The trachea, larynx and main bronchi with the right vagus nerve and nodose ganglion were isolated from guinea-pigs passively immunized 24 h previously with serum containing antiovalbumin antibody. 2. The airways were placed in one compartment of a Perspex chamber for recording of isometric tension while the nodose ganglion and attached vagus nerve were pulled into another compartment. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in the ganglion. Mechanosensitivity of the nerve endings was quantified using calibrated von Frey filaments immediately before and after exposure to antigen (10 ,ug ml-' ovalbumin). 3. Ten endings responded to the force exerted by the lowest filament (0-078 mN) and were not further investigated. In airways from thirteen immunized guinea-pigs, the mechanical sensitivity of Ad afferent fibres (conduction velocity = 4-3 + 0'6 m s-') was enhanced 4-1 + 0¢9-fold following airway exposure to antigen (P < 0 005). Mechanical sensitivities of afferent fibres (conduction velocity = 4-3 + 0-6 m s-1) from non-immunized control guineapig airways were unaffected by antigen (n = 13). 4. Antigen did not overtly cause action potential generation except in one instance when the receptive field was located over the smooth muscle. This ending also responded to methacholine suggesting that spatial changes in the receptive field, induced by muscle contraction, were responsible for the activation. 5. The mediators responsible for these effects are unknown, although histamine, prostaglandins, leukotrienes and tachykinins do not appear to be essential. The increase in mechanical responsiveness was not associated with the smooth muscle contraction since leukotriene C4, histamine and tachykinins, which all caused a similar contraction to antigen, did not affect mechanical thresholds. Moreover, the antigen-induced increases in excitability persisted beyond the duration of the smooth muscle contraction. 6. These results demonstrate that antigen-antibody-mediated inflammatory processes may enhance the excitability of vagal afferent nerve terminals projecting from the airway and thus may contribute to the pathophysiology of allergic airway diseases.

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Histamine enhances vagal pulmonary C-fiber responses to capsaicin and lung inflation

Cited by 64 publications

References 17 publications

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators.

Immunomodulation of afferent neurons in guinea‐pig isolated airway.

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