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DOI: 10.1055/s-2005-918203
© Georg Thieme Verlag Stuttgart · New York
Mechanismen zur Beeinflussung der Zellphysiologie als Wundheilungskonzept
Mechanisms Influencing Cellular Physiology as a Concept of Treatment for Wound Healing DisturbancesPublikationsverlauf
Publikationsdatum:
29. Dezember 2005 (online)
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Zusammenfassung
Ziel: Neues Verständnis über Reparaturmechanismen in verschiedenen Gewebetypen ist die Grundlage aktueller therapeutischer Bemühungen. Im Zentrum vieler experimenteller und auch klinischer Ansätze steht die Beeinflussung der Angiogenese, die sicherlich auch im Kontext der Wundheilung von grundlegender Bedeutung ist. Sowohl die Applikation von Wachstumsfaktoren, als auch der Gentransfer oder die Anwendung genetisch manipulierter Zellen verfolgen häufig dieses Ziel. Der jedoch teilweise unkalkulierbare Effekt auf die induzierte Angiogenese führt auch zu sekundären Problemen wie einer Hyperpermeabilität, die von Gewebsödemen gefolgt zu einer Verschlechterung des Wundmilieus beitragen kann. Wir haben nach Mechanismen zur Beeinflussung der endothelialen Schrankenstörung gesucht. Methodik: In einer ersten experimentellen Untersuchung an kultivierten Endothelzellen verschiedener Herkunft haben wir untersucht, ob die Plasmatransglutaminase (Faktor XIII) einen Einfluss auf die endotheliale Barrierefunktion hat. In einer zweiten Untersuchung wurde der Einfluss der Plasmatransglutaminase unter klinischen Bedingungen an Patienten mit einem chronisch venösen Ulcus cruris untersucht. Ergebnisse: Der aktivierte FXIII (FXIIIA*) führte zu einer Dosis-abhängigen Verminderung der basalen Permeabilität der Endothelzellen um 30 % im Vergleich zur Kontrolle mit einer Maximalwirkung bei Konzentrationen zwischen 1 und 5 U/ml. Im Rahmen der klinischen Untersuchung konnten wir eine fast völlige Reduktion der initialen Hypersekretion im Wundbereich beobachten. Schlussfolgerung: Im experimentellen Ansatz konnten wir nachweisen, dass der aktivierte Faktor XIII die endotheliale Barriere stabilisiert und sogar gegen eine induzierte Hyperpermeabilität schützt. Die klinische Untersuchung zeigte, dass die Plasmatransglutaminase auch bei der lokalen Wundbehandlung zu einer Verminderung der Wundsekretion als Folge einer Barrierestörung führt. Somit könnte dieser Faktor eine therapeutische Option des lokalen oder generalisierten Leakage-Syndroms darstellen.
Abstract
Aim: Recent knowledge about repair mechanisms in different types of tissue is the basic of actual therapeutic efforts. Center of several experimental and clinical approaches is the influencing of angiogenesis with an also distinct meaning concerning wound healing. Therefore, application of growth factors, gene transfer, and employment of genetically manipulated cells often aim at angiogenesis. Nevertheless, manipulation of angiogenesis also leads to secondary problems such as hyperpermeability followed by impairment of local wound milieu. Our study was done to identify mechansims to protect from disturbances of endothelial barrier function. Method: In a first experimental investigation on cultured endothelial cells, the influence of plasma-transglutaminase (Factor XIII) to endothelial barrier function was studied. In a second step, the influence of Factor XIII on wound healing properties was investigated in patients with a chronic venous ulceration. Results: Activated Factor XIII (FXIIIA*) led to a dose-dependent reduction of endothelial cell permeability of 30 % compared to control with a maximum effect using 1 to 5 U/mL. Clinical investigation revealed a nearly complete reduction of wound secretion. Conclusion: Experimental studies revealed that activated Factor XIII stabalizes endothelial barrier under basic conditions as well as under conditions of induced hyperpermeability. Clinical study revealed that Factor XIII also distinctly reduces wound secretion. Therefore, plasma-transglutaminase may offer a new therapeutic option to treat the local or generalized leakage-syndrome.
Schlüsselwörter
endotheliale Barriere - Permeabilität - Wachstumsfaktor - Gentransfer - Faktor XIII
Key words
endothelial barrier - permeability - growth factors - gene transfer - factor XIII
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Prof. Dr. med. G. Wozniak
Klinik für Gefäßchirurgie · Knappschaftskrankenhaus
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46242 Bottrop
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