Abstract
The adhesion of circulating leukocytes to the vascular endothelium is a constant accompaniment of arteriosclerosis and precedes the formation of foam cells and sclerotic plaques. Using an in vivo hamster model with a microscopy chamber implanted in the superficial muscle of the back, it is possible to quantify haemodynamic parameters, blood flow velocity and leukocyte-endothelium interaction in arterioles and post-capillary venoles. Systemic administration of oxidatively modified low density lipoprotein (oxLDL) stimulated the interaction of leukocytes with the endothelium of the microvasculature. Injection of native LDL had no effect. However, pretreatment with either the leukotriene biosynthesis inhibitor MK886, or a fish oil diet supplement, prevented this stimulatory effect of oxLDL. MK866 inhibits the enzyme 5-lipoxygenase, whereas fish oil contains a competitive substrate for this enzyme which leads to a compound with reduced chemotactic or adhesion-inducing activity. It is concluded that leukotriene biosynthesis plays a key role in the development of arteriosclerosis, and that this mechanism is stimulated by oxLDL. Intravital microscopy could provide a very useful model in which to assess various therapeutic applications in the treatment of arteriosclerosis.
Zusammenfassung
Die Adhäsion zirkulierender Leukozyten am vaskulären Endothel geht der Entstehung atherosklerotischer Veränderungen voraus [1, 2]. Aufgrund von invitro-Untersuchungen wurde ein ursächlicher Zusammenhang zwischen der oxidativen Modifikation von Low density lipoproteins (LDL) und der chemotaktischen Akkumulation und Steigerung der Adhäsion von Leukozyten am Endothel postuliert [3, 4]. Um diesen Zusammenhang in vivo zu verifizieren, haben wir ein experimentelles Modell entwickelt, welches die intravitalmikroskopische Visualisierung und quantitative Analyse der Leukozyten/Endothelinteraktion nach Stimulation mit systemisch verabreichten, oxidativ modifizierten, humanen Low density lipoproteins (oxLDL) im Hamster ermöglicht [5]. Dieser Beitrag faßt die Ergebnisse zweier Studien zusammen, in denen gezeigt wurde, daß Leukotriene in der durch oxLDL ausgelösten Leukozytenadhärenzsteigerung eine entscheidende Rolle als Mediatoren übernehmen [6, 7].
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© 1992 Springer Fachmedien Wiesbaden
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Lehr, H.A., Hübner, C., Kohlschütter, A., Messmer, K. (1992). An intravital microscopic investigation of leukocyte adhesion to the microvascular endothelium following intravenous administration of oxidated human low density lipoprotein (oxLDL). In: Heinle, H., Schulte, H., Schaefer, H.E. (eds) Arteriosklerotische Gefäßerkrankungen. Vieweg+Teubner Verlag, Wiesbaden. https://doi.org/10.1007/978-3-663-19646-4_33
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DOI: https://doi.org/10.1007/978-3-663-19646-4_33
Publisher Name: Vieweg+Teubner Verlag, Wiesbaden
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