Morphin hemmt die Expression von Komplementrezeptoren sowie Phagozytose und Oxidativen Burst in Monozyten über einen NO-abhängigen Mechanismus

 

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Zusammenfassung

Ziel der Studie: Monozyten übernehmen durch Erkennung, Ingestion und Vernichtung von Mikroorganismen eine wichtige Funktion in der Immunabwehr. In dieser Untersuchung wurde durchflusszytometrisch der Einfluss von Morphin und Fentanyl auf Phagozytoseaktivität, Produktion reaktiver Sauerstoffmetabolite und Expression der Phagozytose-relevanten Komplementrezeptoren CD11b und CD35 auf der Monozytenoberfläche in einem Vollblutassay untersucht. Methodik: Vollblut von gesunden Probanden (n = 13) wurde mit verschiedenen Morphin- und Fentanylkonzentrationen inkubiert. Die Expression von Rezeptoren auf der Zelloberfläche wurde mittels Fluorochrom-markierter Antikörper bestimmt, die Phagozytoseaktivität anhand der Ingestion fluoreszierender Bakterien gemessen und der Oxidative Burst mittels Dihydrorhodamin-Umwandlung ermittelt. Ergebnisse: Morphin inhibierte zeit- und konzentrationsabhängig alle gemessenen Parameter. Diese Effekte konnten sowohl durch Naloxon als auch durch NO-Synthaseinhibitoren aufgehoben werden. Fentanyl beeinflusste weder in klinisch relevanten noch in supraklinischen Konzentrationen die Expression von Rezeptoren auf der Zelloberfläche, den Oxidativen Burst oder die Phagozytoseaktivität. Schlussfolgerung: Die Ergebnisse lassen vermuten, dass die Morphin-induzierte Hemmung der Monozytenfunktion durch einen µ-Opiatrezeptor auf der Zelloberfläche vermittelt wird. Als second messenger in diesem Prozess dient NO. Fentanyl hingegen beeinflusst die Monozytenaktivität nicht.

Abstract

Objective: Monocytes play a crucial role in the immune response by recognition, ingestion, and intracellular killing of microorganisms. We investigated whether morphine and fentanyl influence CD 11b and CD35 surface receptor expression, phagocytic activity and superoxide anion generation of monocytes in a whole blood flow cytometric assay. Methods: Whole blood of 13 healthy volunteers was incubated with different morphine and fentanyl concentrations. Expression of surface receptors CD 11b and CD35 was determined by fluorochrome-labelled antibodies. Phagocytic activity was assessed by ingestion of fluorescent bacteria. Conversion of dihydrorhodamin served for oxidative burst measurements. Results: Morphine inhibited monocyte function in a concentration and time dependent manner. Morphine-induced changes were abolished by preincubation with the NO synthase inhibitor N-nitro-l-arginine as well as naloxone. Fentanyl failed to inhibit receptor expression, phagocytosis and reactive oxygen production by monocytes in clinically relevant as well as supraclinical concentrations. Conclusion: Our results suggest that these monocyte functions are inhibited by a morphine-stimulated NO release mediated by a µ opiate receptor subtype expressed on the surface of monocytes. In contrast, fentanyl did not share morphine’s inhibitory effects on monocyte activity.

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PD Dr. med. Ingeborg Welters

Abteilung für Anästhesiologie, Intensivmedizin und Schmerztherapie · Universitätsklinikum Gießen

Rudolf-Buchheim-Straße 7 · 35385 Gießen

Email: Ingeborg.D.Welters@chiru.med.uni-giessen.de