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Molekularbiologische Grundlagen der Gastroenterologie pp 322–332Cite as

Rolle des NO bei entzündlichen Erkrankungen des Gastrointestinaltrakts

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Zusammenfassung

Die Stickoxid(NO-)biosynthese durch Leukozyten und Gewebezellen spielt bei der Regulation von Entzündungsreaktionen eine wichtige Rolle. NO bewirkt eine Vasodilatation und hemmt die Adhäsion von Thrombozyten und Leukozyten am Endothel, wodurch eine optimale Durchblutung gewährleistet ist. Je nach Entzündungsmodell können andere Prozesse wie die Ödembildung oder die Migration der Entzündungszellen durch die NO-Biosynthese positiv oder negative beeinflußt werden. Im Netzwerk zellulärer Kommunikation wirkt NO als parakriner und autokriner Signalstoff, beeinflußt aber auch die Freisetzung anderer Mediatoren, wie die Produktion der Eicosanoide. Eine direkte Zellschädigung durch NO kann durch die Inhibition der mitochondrialen Atmung oder durch eine Schädigung der DNA hervorgerufen werden.

Bei Infektionen unterstützt das NO das Abwehrsystem durch seine antimikrobielle Wirkung. Im Rahmen septischer Verläufe kann eine überschießende NO-Produktion aber auch zur Entwicklung des hyperdynamen Schocks, der Kardiomyopathie und der Leberzellinsuffizienz beitragen. Eine Beeinträchtigung des Leberstoffwechsels durch die NO-Biosynthese dürfte auch bei lokalen Entzündungsreaktionen wie bei Hepatitiden und bei Abstoßungsreaktionen von Bedeutung sein. Bei Autoimmunerkrankungen wurde ebenfalls eine Aktivierung der NO-Biosynthese nachgewiesen. In der Patho-physiologie des Diabetes mellitus scheint NO sowohl eine Inhibition der Insulinfreisetzung als auch die direkte Zerstörung der Inselzellen hervorzurufen. Auch bei Patienten mit Colitis ulcerosa ist die NO-Produktion erhöht. Die funktionelle Bedeutung dieser Beobachtung ist allerdings noch unklar.

Summary

Biosynthesis of nitric oxide (NO) plays an important role in the regulation of inflammatory responses. NO is a potent vasodilator and inhibits the adhesion of thrombocytes and leukocytes at the endothelium, ensuring optimal perfusion of the inflammed tissue. Depending on the experimental model of inflammation other aspects such as vascular leakage or migration of leukocytes may be stimulated or suppressed by NO synthesis. Within the network of cellular communication NO acts as a paracrine and autocrine mediator, but also affects the production of other mediators, including eicosanoids and oxygen radicals. Direct toxicity of NO is based on the inhibition of mitochondrial respiration and damage of the DNA.

In the case of infection NO supports the immune system by its antimicrobial activity. However, overproduction of NO during septic courses contributes to the development of hyperdynamic shock, septic cardiomyopathy and hepatocellular insufficiency. NO biosynthesis may also interfere with metabolic performane of the liver during lokal inflammatory responses of hepatitis or rejection episodes following liver transplantation. Induction of NO biosynthesis was also demonstrated in autoimmune diseases such as diabetes mellitus type I and ulcerative colitis. In the pathophysiology of diabetes mellitus NO not only inhibits the release of insulin but may also be responsible for the destruction of pancreatic islet cells. The functional relevance of NO production in ulcerative colitis remains to be uncovered.

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Authors
  1. J. Stadler
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Editors and Affiliations

  1. Chirurgische Klinik I, Universität Ulm, Steinhövelstr. 9, 89075, Ulm, Deutschland

    Hans G. Beger

  2. Abteilung Gastroenterologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Str. 8, 30625, Hannover, Deutschland

    Michael P. Manns

  3. I. Medizinische Universitäts-Klinik, Martinistr. 52, 20251, Hamburg, Deutschland

    Heiner Greten

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© 1995 Springer-Verlag Berlin Heidelberg

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Stadler, J. (1995). Rolle des NO bei entzündlichen Erkrankungen des Gastrointestinaltrakts. In: Beger, H.G., Manns, M.P., Greten, H. (eds) Molekularbiologische Grundlagen der Gastroenterologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79782-8_31

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  • DOI: https://doi.org/10.1007/978-3-642-79782-8_31

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