Die sensible Atemwegsinnervation und die Tachykinine bei Asthma und chronisch-obstruktiver Lungenerkrankung (COPD)

Zusammenfassung

Mit der Identifizierung und Charakterisierung von zahlreichen neuronalen Mediatoren gewann die Forschung der Innervierung der Atemwege in den letzten Jahren zunehmend an Bedeutung. Eine Reihe von Stimuli wie Capsaicin, Bradykinin, hyperosmotische Salzlösung, Zigarettenrauch, Allergene, Ozon, pro-inflammatorische Mediatoren und kalte trockene Luft sind in der Lage, sensible Atemwegsneurone zu aktivieren. Allergene können eine Freisetzung von Substanz P (SP) and Neurokinin A (NKA) induzieren. SP wird in den Zellkörpern der Atemwegsneurone des Ganglion trigeminale, des Ganglion jugulare und des Ganglion nodosum synthetisiert. Tachykinine haben einen pro-inflammatorischen Effekt auf die Atemwege und sind an neurogenen Entzündungen in den Atemwegen beteiligt. Weitere Tachykinine wie Virokinin und Hemokinin wurde vor kurzem entdeckt und charakterisiert. In den Atemwegen werden Tachykinine nach ihrer Freisetzung von Neutraler Endopeptidase (NEP) und einem angiotensinumwandelnden Enzym abgebaut. Tachykinine steuern den Tonus der glatten Atemwegsmuskulatur, die Schleimsekretion, die bronchialen Blutzirkulation sowie die Immunzellen nach Aktivierung des Neurokinin-1-(NK-1)- oder Neurokinin-2-(NK-2)-Rezeptors und sind vermutlich an der Pathogenese von Asthma bronchiale und COPD beteiligt. Während unterschiedliche Aspekte der neurogenen Entzündung im Tiermodell bisher mehr untersucht wurden, ist über die Rolle der neurogenen Atemwegsentzündung beim Menschen wenig bekannt. Um die genauere Rolle der sensiblen Atemwegsinnervation und der Tachykinine bei chronisch-entzündlichen Atemwegserkrankung wie Asthma bronchiale und COPD verstehen zu können, sind in Zukunft jedoch weitere Studien im Hinblick auf die Aktivierung der sensiblen Nervenfasern und die Interaktion zwischen Entzündungszellen und Atemwegsneuronen erforderlich.

Abstract

The airway nerve has gained importance in the field of respiratory research as it is known to have the capacity to release numerous mediators which can cause pulmonary effects in the airways. Meanwhile, a broad range of stimuli including capsaicin, bradykinin, hyperosmolar saline, tobacco smoke, allergens, ozone, inflammatory mediators and cold dry air have been shown to activate sensory nerve fibres to release neuropeptides such as the tachykinins substance P (SP) and neurokinin A (NKA) to mediate neurogenic inflammation. SP is synthesized in cell bodies of airway neurons of the trigeminal, jugulare and nodose ganglia. Following their release, tachykinins are degraded by neutral endopeptidase (NEP) and an angiotensin-converting enzyme. Tachykinins have been proposed to play an important role in human respiratory diseases such as bronchial asthma und chronic obstructive diseases (COPD) as they have been shown to have potent effects on the tone of airway smooth muscle, airway secretions, bronchial circulation and on inflammatory and immune cells by activation of the neurokinin-1 (NK-1) and neurokinin-2 (NK-2) receptors. Recently, new tachykinins such as virokinin and hemokinin were identified and characterised. Different aspects of the neurogenic inflammation have been well studied in animal models of allergic airway inflammation, but only little is known about the role of neurogenic airway inflammation in human diseases. To address the precise role of tachykinins and airway sensory nerves in human asthma und COPD, experiments on sensory nerve sensitisation and neuro-immune interaction have to be carried out in future studies.

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