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DOI: 10.1055/s-2004-821178
Georg Thieme Verlag KG Stuttgart · New York
Vermehrte Expression der induzierbaren NO-Synthase (iNOS) in Makrophagen des Plazentabettes bei schwerer Präeklampsie
Increased Expression of iNOS in Macrophages of the Placental Bed of Women with Severe PreeclampsiaPublication History
Publication Date:
02 September 2004 (online)
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Zusammenfassung
Fragestellung: Im Zentrum der Pathogenese der Präeklampsie steht die inadäquate Ausbildung uteroplazentarer Gefäße, bedingt durch gestörte Trophoblastinvasion und mangelhafte Vasodilatation. In diesem Zusammenhang spielen proapoptotische Effekte (TNF-α-Sekretion; Tryptophanmangel) von Makrophagen in der Media der Spiralarterien sowie periarteriell eine bedeutende pathogenetische Rolle. Ziel dieser Untersuchung war es zu klären, ob diese Makrophagen im Plazentabett bei Patientinnen mit schwerer Präeklampsie Stickstoffmonoxid (NO) exprimieren, da NO in der Lage ist, Apoptose zu induzieren.
Material und Methodik: An seriellen Kryostat- und Paraffinschnitten von Plazentabettbiopsien präeklamptischer Patientinnen (n = 7; Spiralarterien n = 42) und gesunder normotensiver Schwangerer (n = 8; Spiralarterien n = 57) wurden immunhistochemisch Trophoblastzellen, Makrophagen und iNOS-exprimierende Zellen dargestellt.
Ergebnisse: a) Sowohl die Anzahl der Makrophagen in der Media der Spiralarterien (p = 0,02) als auch die Anzahl der iNOS-exprimierenden Makrophagen (p < 0,001) war bei Präeklampsie signifikant erhöht im Vergleich zu gesunden Schwangeren. b) Plazentabettbiopsien normotensiver Schwangerer zeigten signifikant weniger periarterielle Makrophageninfiltrate als Biopsien präeklamptischer Patientinnen (p = 0,001). In diesen Makrophageninfiltraten konnte nur bei Präeklampsie eine iNOS-Expression nachgewiesen werden (p < 0,001).
Schlussfolgerung: Bei Präeklampsie könnten in der Media sowie periarteriell lokalisierte Makrophagen die Apoptose invadierender extravillöser Trophoblastzellen durch eine lokal im Plazentabett signifikant erhöhte NO-Synthese induzieren und somit zur inadäquaten endovaskulären Trophoblastinvasion beitragen.
Abstract
Purpose: Impaired invasion of uteroplacental arteries by extravillous trophoblast cells is a key pathogenetic mechanism of preeclampsia. In this context proapoptotic effects (secretion of TNF-α; tryptophan depletion) of macrophages in and around the wall of spiral arteries may play a crucial role. The aim of this study was to assess whether these macrophages in the placental bed of women with severe preeclampsia express NO, which is known to trigger apoptosis in other tissues.
Material and Methods: Serial cryostate and paraffin sections were obtained using placental bed biopsies of preeclamptic patients (n = 7; spiral arteries n = 42) and normotensive healthy controls (n = 8; spiral arteries n = 57) and immunostained for trophoblast cells, macrophages and iNOS.
Results: a) The number of macrophages in the media of spiral arteries (p = 0.02) as well as the iNOS expression in these cells (p < 0.001) was significantly increased in preeclamptic women compared to normotensive controls. b) Placental bed biopsies of normotensive controls showed significantly less infiltrates of macrophages around the spiral arteries than biopsies obtained from preeclamptic women (p = 0.001). These infiltrates revealed an iNOS expression only in cases of preeclampsia (p < 0.001).
Conclusion: Our data suggest that the impaired endovascular invasion of uteroplacental arteries by extravillous trophoblast cells in preeclampsia could be triggered by apoptotic effects via a significantly increased NO synthesis controlled by macrophages in and around the spiral arteries in the placental bed.
Schlüsselwörter
Präeklampsie - Plazentabett - Makrophagen - iNOS - Apoptose
Key words
Preeclampsia - placental bed - macrophages - iNOS - apoptosis
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1 Autoren teilen Erstautorenschaft
Univ.-Prof. Dr. med. Werner Rath
Frauenklinik für Gynäkologie und Geburtshilfe
Universitätsklinikum Aachen
Pauwelsstraße 30
52074 Aachen
Email: wrath@ukaachen.de
Email: bhuppertz@ukaachen.de