Treatment with proteolytic enzymes inhibits vascular allograft rejection in rats
Gaciong Z.1, Paczek L.1, Bojakowski K.1, Wisniewski M.1, Lao M.1,
Heidland A.2. Treatment with proteolytic enzymes inhibits vascular
allograft rejection in rats. Inter Journal of
Tissue Reactions 1997,
Vol. XIX, No.1/2, Abst. 120,
pp. 96, ISSN 0250-0868 149K/245 (19-04-2).
1 Transplantation Institute, Warsaw School of Medicine, Warsaw,
Poland. 2 University of Wuerzburg, Germany.
7th Interscience World Conference on Inflammation, Antirheumatics,
Analgesics, Immunomodulators, Geneva, Switzerland, 19-21 May
Abstract
Chronic rejection is characterised by vascular changes (transplant
arteriosclerosis) which represent a process of vascular remodelling
induced by non-immune and immune injury. Recently it has been shown
that protease therapy ameliorates certain immune-mediated diseases.
We studied the effect of administration of active proteases on
aortic transplant arteriosclerosis in rats.
Methods
Segments of abdominal aorta from SHR rats were transplanted
orthotopically into WKY recipients (MHC class I discordant). Two
groups of allografted rats were used: one group (n = 8) was treated
with daily intraperitoneal injections of 12 mg Phlogenzym®
(trypsin, bromelin, rutosid), the other group (n = 8) received
placebo. Eight WKY rats were transplanted with syngeneic aortas and
treated with placebo. After 8 weeks structural changes of the
grafted segment were estimated by morphometric analysis of
formalin-fixed sections with specific stains.
Results
In untreated allografts there were a marked intima thickening,
medial necrosis with disruption of elastin fibers and inflammatory
infiltrates in the adventitia. Administration of proteases inhibited
formation of neointima by 59.0 % when cross-sectional areas were
compared (80 ± 11 versus 195 ± 11 mm2 , p<0.01 ; protease vs placebo
treated allograft recipients, respectively) and decreased medial
injury as estimated by the integrity of elastin fibers and smooth
muscle cell density.
Conclusion
In an experimental model of vascular rejection protease
administration inhibits arterial wall remodeling.