Substance-P-lnduced Histamine Release from Human Nasal Mucosa in vitro

Schierhorn, Katrin; Brunnée, T.; Schultz, Klaus-Detlev; Jähnke, V.; Kunkel, G.

doi:10.1159/000236946

Cited by 24 publications

(4 citation statements)

References 17 publications

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“…Unfortunately, very little work on specifically human nasal mucosa has been reported. Previously, we described a culture system of human nasal mucosa (12,13) on gelatin sponges at the air-liquid interface.…”

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confidence: 99%

Influence of Ozone and Nitrogen Dioxide on Histamine and Interleukin Formation in a Human Nasal Mucosa Culture System

Schierhorn

Zhang

Matthias

et al. 1999

Am J Respir Cell Mol Biol

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There is evidence that asthma and other allergic diseases are increasing and air pollution has been considered an important contributing factor to this observation. Using a specially designed organ culture system, we examined the influence of ozone (0.06 to 0. 2 ppm) and nitrogen dioxide (NO2, 200 and 800 micrograms/m3) on nasal mucosa exposed for 24 h. Tissue was obtained from 105 patients undergoing surgical therapy (septoplasty and reduction of the inferior turbinates) for chronic nasal obstruction. The histamine content in the culture medium of ozone- and NO2-exposed samples was significantly elevated compared with the control cultures. This elevation was correlated with the number of degranulated mast cells in the tissue determined by histomorphometry (P < 0.001). Moreover, the cytokines interleukin (IL)-1beta (P < 0.05), IL-6 (P < 0.01), IL-8 (P < 0.001), and tumor necrosis factor-alpha (TNF-alpha, P < 0. 001) were significantly increased (ozone 0.1 ppm). Furthermore, we found significant increases in the release of IL-4, IL-6, IL-8, and TNF-alpha of ozone-exposed (0.1 ppm) samples of atopic versus nonatopic patients and to a lesser extent for histamine following exposure to 0.15 ppm ozone. These results indicate that low ozone concentrations and NO2 lead to an inflammation of human nasal mucosa in vitro and that priming factors such as atopy or preexisting inflammation do increase the sensitivity to ozone and NO2. This organ culture system proved to be a good experimental design for studying pathophysiologic alterations of human nasal mucosa under different experimental conditions (e.g., air pollutants).

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confidence: 99%

Influence of Ozone and Nitrogen Dioxide on Histamine and Interleukin Formation in a Human Nasal Mucosa Culture System

Schierhorn

Zhang

Matthias

et al. 1999

Am J Respir Cell Mol Biol

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“…Schierhorn et al [16] reported that SP induced histamine release from mast cells into the human nasal mucosa. In addition, the effects of neurotransmitters were greatly influenced by their splitting enzyme [17].…”

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confidence: 99%

Nasal Challenge Activates the Mucociliary Transport System on Not Only the Ipsilateral but also the Contralateral Side of the Nose in Patients with Perennial Allergic Rhinitis

Fujieda¹,

Kimura²,

Takahashi³

et al. 2000

ORL

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It is controversial whether the mucociliary transport system in the nasal mucosa of persons with allergic rhinitis is upregulated after an allergen challenge in vivo. The aim of this study was to assess the effect of a specific allergen challenge on the mucociliary transport system in allergic rhinitis. We used a challenge of house dust mites or a control substance on one side of the nose of 97 volunteers (54 with allergic rhinitis for house dust mites and 43 without allergies). The mucociliary transport system of the ipsilateral or contralateral side of the nose challenged was evaluated using the saccharin clearance time on the right side of the nose. The saccharin clearance time was significantly shortened after an allergen challenge not only on the ipsilateral (right) side of the nose (from 15.0 ± 11.6 to 10. 9 ± 9.2 min, mean ± SD, p = 0.041) but also on the contralateral (left) side of the nose (from 14.7 ± 10.1 to 8.1 ± 7.9 min, p = 0.013) in the allergic group. A reduction of the saccharin clearance time was also seen in the allergic group after a control challenge [ipsilateral (right) challenge: from 13.0 ± 10.0 to 11.6 ± 10.6 min, contralateral (left) challenge: from 13.5 ± 9.0 to 10.2 ± 10.1 min]. There were no reductions of the saccharin clearance time after an allergen or control challenge in the nonallergic groups. These results suggest that a unilateral nasal challenge accelerates the mucociliary transport system bilaterally in the nose of subjects with a hypersensitivity such as allergic rhinitis.

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“…There is anatomical support for this contention since sensory nerves have been found near mast cells in various tissues including the airways [45]. SP, or stable analogs thereof, have been shown to elicit histamine release from guinea pig lungs in vivo [46] and human pulmonary mast cells [47] and nasal mucosa in vitro [48]. In our own studies SP-induced plasma protein extravasation in guinea pig airways was apparently not mediated by histamine (which may have been released from mast cells in response to the neuropeptide) since a maximally effective dose of pyrilamine did not modify the effect.…”

Section: Discussionmentioning

confidence: 99%

A Role for Histamine and Substance P in Immediate Allergic Responses in Guinea Pig Airways: Characterization of MDL 108,207DA, a Dual H<sub>1</sub> / NK-1 Receptor Antagonist

Kudlacz¹,

Shatzer²,

Logan³

et al. 1998

Int Arch Allergy Immunol

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Background: Histamine is a critical mediator of immediate hypersensitivity reactions. Sensory neuropeptides, such as substance P (SP), may also contribute to acute inflammatory responses. A compound which antagonizes both H₁ and NK-1 receptors, such as MDL 108,207DA, may present a significant therapeutic advantage over pure antihistamines. Methods: The binding affinity of MDL 108,207DA for H₁ and NK-1 receptors was evaluated and its potency of antagonism evaluated in vitro. The in vivo antagonism of SP- or histamine-induced microvascular leakage in guinea pig airways was examined. A role for these mediators in antigen-induced microvascular leakage in ovalbumin-sensitized guinea pig airways was examined using MDL 108,207DA as well as the NK-1-selective antagonist FK888 and the H₁-selective antagonist pyrilamine alone or in combination. Results: The affinity of MDL 108,207DA for H₁ and NK-1 receptors is similar to that of receptor-selective antagonists. The compound inhibits both receptors in vitro and in vivo with comparable potencies for each. The efficacy of FK888 in combination with pyrilamine and MDL 108,207DA on antigen-induced microvascular leakage in sensitized guinea pig airways supports a role for both SP and histamine in early allergic responses. Conclusion: The contribution of both SP and histamine to immediate hypersensitivity reactions supports the utility of NK-1 and H₁ receptor antagonist therapy. MDL 108,207DA incorporates both activities into the same compound and, as a result, may be useful in the treatment of allergic diseases.

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Substance-P-lnduced Histamine Release from Human Nasal Mucosa in vitro

Cited by 24 publications

References 17 publications

Influence of Ozone and Nitrogen Dioxide on Histamine and Interleukin Formation in a Human Nasal Mucosa Culture System

Influence of Ozone and Nitrogen Dioxide on Histamine and Interleukin Formation in a Human Nasal Mucosa Culture System

Nasal Challenge Activates the Mucociliary Transport System on Not Only the Ipsilateral but also the Contralateral Side of the Nose in Patients with Perennial Allergic Rhinitis

A Role for Histamine and Substance P in Immediate Allergic Responses in Guinea Pig Airways: Characterization of MDL 108,207DA, a Dual H<sub>1</sub> / NK-1 Receptor Antagonist

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