Inhibition of semicarbazide-sensitive amine oxidases decreases lymphocyte infiltration in the early phases of rat liver allograft rejection.
Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation in vitro and in vivo. VAP-1 is also an ectoenzyme with semicarbazide-sensitive amine oxidase (SSAO) activity. In this study we investigated whether inhibition of SSAO influences the inflammatory infiltration in acute rat liver allograft rejection. BN recipients of DA liver allografts were treated with 50 mg/kg/d semicarbazide, an inhibitor of SSAO, or similar volumes of saline. 10 rats/group were followed for graft survival, and 10 rats/group were sacrificed on day 7 post-transplantation for histology and T-lymphocyte isolation. The area percentage of portal inflammatory infiltrates in the grafts was assessed from digital photomicrographs. The proportion of CD4-, CD8- and IL2-receptor positive lymphocytes in the graft was quantified with flow cytometry. On day 7, semicarbazide treatment significantly decreased the inflammatory infiltrate area in the grafts. CD4-, CD8- and IL2-receptor positive cells were equally affected. However, animal survival was not affected. Blockade of the enzymatic activity of VAP-1 has a significant effect on lymphocyte infiltration early in acute liver rejection. Later, activation of other adhesion pathways can by-pass the blockade caused by VAP-inhibition.
Martelius
T
T
Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. timi.martelius@helsinki.fi
Salmi
M
M
Krogerus
L
L
Loginov
R
R
Schoultz
M
M
Karikoski
M
M
Miiluniemi
M
M
Soots
A
A
Höckerstedt
K
K
Jalkanen
S
S
Lautenschlager
I
I
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006084:Graft Rejection; D007150:Immunohistochemistry; D016031:Liver Transplantation; D051381:Rats; D014184:Transplantation, Homologous
D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D006631:Amine Oxidase (Copper-Containing); C510433:vascular adhesion protein-1, rat